Are many or even most of the health challenges in modern Western societies—high blood pressure, high blood sugar, high cholesterol levels, cardiovascular disease in general, weight problems, etc.—related? There is a good case to be made that they are.

At the core of Syndrome X, now much more commonly known as the metabolic syndrome, are dysregulations and dysfunctions involving glucose and insulin. These manifest as central obesity (excessive fat around the belly), high blood pressure and blood fat disorders—especially hypertriglyceridemia and low levels of HDL cholesterol. In addition to participating in the development of many facets of the metabolic syndrome, impairment in insulin sensitivity also appears to be involved in the aging process by promoting inflammation, endothelial dysfunction (problems with the blood vessels), the production of advanced glycation end products (AGE) and oxidative stress. Downstream consequences of these dysfunctions include cardiovascular disease and cancer. These issues were discussed approximately one year ago in this magazine under the heading “Is the Metabolic Syndrome a Consequence of Aging?” (May 2017) Nonalcoholic fatty liver disease was not originally included in metabolic syndrome manifestations. However, over the past decade medical thinking by almost all parties regarding the relationship of these conditions has moved strongly towards viewing them as linked in some way. From 15 to 33 percent of the worldwide population is estimated to suffer from non-alcoholic fatty liver disease.

As noted in the earlier article, major questions remain regarding the early appearance of the metabolic syndrome. Western medicine, unlike, for instance, traditional Chinese and Indian medicine, tends to pursue and treat the various arms of the metabolic syndrome as distinct clinical entities. Much of the research on the syndrome within allopathic medicine over the past three decades has been aimed at arguing against this separation. Questions regarding the liver and metabolic syndrome involve similar issues. According to some authorities, non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. However, others believe NAFLD is a distinct entity that actually initiates the metabolic syndrome. The choice as to which comes first, the metabolic syndrome or NAFLD, if indeed they are distinct, helps to determine how each can be prevented and treated.

Early Signs of the Metabolic Syndrome

Most clinicians consider a level of circulating glucose under fasting conditions in the range of 100–125 mg/dl to be prediabetic, but agreement beyond this is hard to come by. Normal levels of blood glucose and circulating insulin, meaning levels that do not lead to components of the metabolic syndrome, remain in dispute. Nevertheless, evidence suggests that surprisingly “normal” fasting blood glucose levels still have consequences.

Circulating glucose within levels generally accepted as normal can influence brain function in an unfavorable manner. Similarly, increasing hemoglobin A1C (HbAlC) and insulin levels even in the non-diabetic range can affect blood pressure adversely. Such observations lead to suspicions that minor insulin resistance predicts the early onset of many disturbed health parameters involved in the metabolic syndrome. Recently, Harry G. Preuss and co-authors, of whom I am one, addressed just such questions in “General Lack of Correlations between Age and Signs of the Metabolic Syndrome in Subjects with Non-diabetic Fasting Glucose Values.”¹

Based on our study, the health data were significantly better with fasting glucose levels in the range of 67–86 mg/dL than at 98–125 mg/dL. Across a wide range of variables lower definitely was better leading to the conclusion that decreasing insulin resistance and maintaining fasting glucose levels at the low end of the normal range is highly desirable. Advancing years did not appear to be a factor leading to the metabolic syndrome. In terms of the present topic, using the data at hand, advancing age per se also did not seem to affect liver health.

Non-Alcoholic Fatty Liver Disease and the Metabolic Syndrome in Non-Diabetics
If aging is not a primary factor in the appearance of the metabolic syndrome, yet NAFLD and the metabolic syndrome are linked, some other cause or causes are at work. The usual list of suspects can be found in the typical elements examined to determine diagnosis.

Aside from ruling out an elevated consumption of alcohol, a verdict of NAFLD primarily is based on discovering excess liver fat accumulation along with raised circulating aminotransferase levels generally involving ALT more than AST. For clarity, the latter are “two important transaminase enzymes…aspartate transaminase (AST), also known as serum glutamic oxaloacetic transaminase (SGOT); and alanine transaminase (ALT), also called alanine aminotransferase (ALAT) or serum glutamatepyruvate transaminase (SGPT)… [Transaminases] are important in the synthesis of amino acids, which form proteins.”² Liver health and function is evaluated by, among other markers, the levels of ALT, ALS and their ratio. Whenever a patient gets blood drawn for basic blood panel tests, ALT and ALS are checked.

Alanine aminotransferase (ALT) found persistently to be elevated often is viewed as indicating the presence of NAFLD. More generally, an elevated circulating concentration of ALT is recognized to be a fairly specific sign for liver injury. In considering the “normal” range of ALT (<40 U/L) for cardiovascular disease in general, unfortunately the normal range does not represent a cut-off below which one is safe, but, instead, a point of a continuum of risk.³

Starting with a subject population that is non-diabetic and without any of the normal signs of liver dysfunction, the question, again, is whether NAFLD is a component of the metabolic syndrome or, instead, is an independent disorder that precedes and actually initiates the onset of the syndrome. The answer to this question has important implications for the treatment of both conditions. On the one hand, if the metabolic syndrome, meaning primarily insulin resistance, is the central issue and NAFLD is really just a component of the syndrome, even should there be feedback once NAFLD is established, then the metabolic syndrome is tackled first to prevent or treat its manifestations in the liver. On the other hand, if the hepatic condition is first in time and in causality, treatment starts with the liver.

Treating NAFLD: The Liver Or Insulin Resistance
A major reason for looking closely at the relationship between the metabolic syndrome and NAFLD is that treating the latter with approaches aimed specifically at the liver has yielded underwhelming levels of success. The single most successful standalone natural ingredient probably is mixed tocotrienols taken 200 mg twice per day for a year.⁴ Overall, 13 of 26 subjects (50 percent) became NAFLD-negative. In those with a mild form, there was a 38 percent decrease in the number of subjects with active disease at the end of the study, indicating that improvement was linked to the severity of the condition. Somewhat less impressive was silybin (an active component of milk thistle extract) combined with phosphatidylcholine and vitamin E acetate (á-tocopherol), again, taken for twelve months. Still, the formula significantly improved liver conditions associated with NAFLD (steatosis, lobular inflammation, ballooning, and fibrosis) and the overall NAFLD Activity Score.⁵ Interestingly, in another trial the results with milk thistle and vitamin E were much improved in patients who followed a low calorie diet with weight loss.⁶

Findings of this sort strengthen the argument that NAFLD is an aspect of the metabolic syndrome and not its cause. A number of studies have demonstrated that hepatic insulin resistance likely is the chief culprit.⁷ For instance, the accumulation of triglycerides in the liver is a cause of the condition. Technically, hyperinsulinemia promotes the upregulation of genes that promote de novo lipogenesis (biosynthesis of fat) in the liver.^8,9

Given evidence that de novo lipogenesis, which primarily is induced by high insulin levels and refined carbohydrates, is an important agent in the development of liver dysfunction, it can come as no surprise that an inhibitor of this process, (–)-hydroxycitric acid (HCA), improves liver function in experimentally-induced nonalcoholic steatohepatitis (NASH), a component of NAFLD. In animal experiments, both liver fibrosis and markers of liver function were improved under experimental conditions with ingestion of HCA.^10,11 It should be noted that, experimentally, liver dysfunction is closely associated with the intake of rapidly absorbed carbohydrates, but not necessarily carbohydrate consumption itself.¹² In humans, short-term fructose consumption in either isocaloric exchange or in hypercaloric supplementation promotes the development of hepatic insulin resistance in non-diabetic adults without affecting peripheral or muscle insulin sensitivity.¹³ Indeed, at this point there is little doubt but that fructose consumption in excess is a primary driver of the synthesis of triglycerides and other perturbations of the handling of fats by the liver leading to fatty liver disease.¹⁴ Fructose appears to induce both NAFLD and metabolic syndrome through related mechanisms.¹⁵ A steadily growing body of evidence supports the position that medium and long-term excess ingestion of fructose and rapidly absorbed carbohydrates progressively distort the handling of glucose and insulin not just in the liver, but also in the muscles and other lean tissues.

Back to the Chicken and Egg Question
So, what do we have so far? Evidence from animal models and human experience indicates that certainly one or more of the drivers of liver dysfunction—fructose and rapidly absorbed carbohydrates—act initially on the liver to cause insulin resistance. Liver insulin resistance subsequently makes general control of blood sugar levels more difficult and causes the body to release more insulin and/or insulin in greater amounts at a given time to regulate blood sugar, an action with particularly unfortunate consequences after meals. Over time, elevated glucose and insulin levels originally caused by the liver lead to insulin resistance in the muscles and other lean tissues, tissues that account for approximately 70 percent of all glucose clearance in the body.

In addition, there is a feedback loop between the liver and peripheral lean tissues that involves the metabolism of fats for energy and storage. Initially, circulating elevated levels of blood glucose result from hepatic insulin resistance whereas increased circulating free fatty acid concentrations are a primary expression of peripheral insulin resistance.¹⁶ Insulin, of course, controls the clearance and energy metabolism of both fuel sources; as a storage hormone, insulin in excess directly impedes the use of fats for energy, hence contributes to elevations in blood free fatty acids and triglycerides. The effects are bidirectional: insulin resistance leads to fat accumulation and fat accumulation amplifies insulin resistance.

This line of argument and supporting evidence suggest that the metabolic syndrome and NAFLD generally are linked from the start and take form largely concurrently. Forthcoming work by the team of Harry Preuss et al, indicates exactly this. ALT and the ratio of AST/ALT correlate significantly with fasting blood glucose in non-diabetics indicating that these markers of liver health move largely in unison with changes in insulin sensitivity. Insulin resistance drives both the metabolic syndrome and NAFLD.

What Is To Be Done?
Key to improving liver health are diet and exercise habits. This fact showed up in the treatment option mentioned above which combined milk thistle with vitamin E—results were much better in the subjects on a low calorie diet. Nutrients such as tocotrienols, milk thistle, quercetin and other liver supports and detoxifiers only marginally address the primary issues. These primary issues include:

• Consumption of rapidly absorbed carbohydrate sources, especially fructose, as discussed in the foregoing text
• Ingestion of foods that lead to elevated insulin release when eaten with refined carbohydrates; these include red meat and branched-chain amino acid sources¹⁷
• Reduced metabolism of fats for energy; certain food combinations, such as fats eaten with rapidly absorbed carbohydrates, severely interfere with the utilization of consumed fats for energy with negative implications for both liver and muscle insulin sensitivity
• Reliance on ultra-processed foods, meaning a preponderance of the foods now eaten in the US and many European nations ^18,19,20 (see “Calories Don’t Add Up“
• A lack of regular exercise: 15–30 minutes twice per day is recommended

For success, the right tool must be applied for the proper purpose. Although it is true that the environment increasingly is polluted with various toxins, NAFLD predominantly is a result of the foregoing issues. Correspondingly, corrective nutrients and herbs for NAFLD, just as with the metabolic syndrome, are those that improve insulin sensitivity, fatty acid metabolism and metabolic fitness.

It also is useful to consider here once again observations made in “Nutrient Combining”

• Low glycemic index diets improve glycemic (blood sugar) response and variability as well as promote the metabolism of fat for energy; they may promote longterm health.^21,22
• Taken in a milkshake, fructose (30 g) increased postprandial lipemia by 37 percent compared with control; glucose (17.5 g) increased postprandial lipemia by 59 percent.²³ (Lipemia is the presence in the blood of an abnormally high concentration of emulsified fat, meaning primarily triglycerides, not cholesterol.)
• In Syndrome X/insulin resistant subjects (BMI of 30), glucose consumption (50 g) led to a 15.9 percent greater glycemic response and a 30.9 percent greater insulin response than did fructose (50 g). This is true in part because fructose is processed in the liver and then released later as glucose and/or converted into fat.
• On an energy balanced diet in these same subjects, fructose compared with glucose increased carbohydrate oxidation 31 percent, but decreased fat oxidation by 39 percent.²⁴
• Low-fat/high-carbohydrate diets in Syndrome X individuals reduce levels of HDL cholesterol and increase triacylglycerol concentrations.²⁵
• Sucrose is glucose + fructose; lactose is glucose + galactose; grape sugar (dextrose) is glucose.

Conclusion
There is an old Chinese medical observation to the effect, “disease enters the body by way of the mouth.” Both the metabolic syndrome and non-alcoholic liver disease would appear to offer evidence for the correctness of this judgment. They also would appear to buttress another ancient opinion, this time from the ancient Greek physician Galen, who considered many of the conditions that today we associate as cardiovascular as arising from the liver and only subsequently manifesting in the heart, the circulation, and so forth. Liver health, as evidenced by subtle changes in certain markers, is closely linked to insulin sensitivity and energy metabolism. As such, the best approach to liver issues that are not related to the ingestion of toxins per se is to be found in diet and exercise habits.

Endnotes

1. Preuss HG, Mrvichin N, Clouatre D, Bagchi D, Preuss JM, Perricone NV, Swaroop A, Kaats GR. General Lack of Correlations between Age and Signs of the Metabolic Syndrome in Subjects with Non-diabetic Fasting Glucose Values. J Am Coll Nutr. 2017 Sep–Oct;36(7):556–64.
2. https://en.wikipedia.org/wiki/Transaminase
3. Porter SA, Pedley A, Massaro JM, Vasan RS, Hoffmann U, Fox CS. Aminotransferase levels are associated with cardiometabolic risk above and beyond visceral fat and insulin resistance: the Framingham Heart Study. Arterioscler Thromb Vasc Biol. 2013 Jan;33(1):139–46.
4. Magosso E, Ansari MA, Gopalan Y, Shuaib IL, Wong JW, Khan NA, Abu Bakar MR, Ng BH, Yuen KH. Tocotrienols for normalisation of hepatic echogenic response in nonalcoholic fatty liver: a randomised placebo-controlled clinical trial. Nutr J. 2013 Dec 27;12(1):166.
5. Loguercio C, Andreone P, Brisc C, Brisc MC, Bugianesi E, Chiaramonte M, Cursaro C, Danila M, de Sio I, Floreani A, Freni MA, Grieco A, Groppo M, Lazzari R, Lobello S, Lorefice E, Margotti M, Miele L, Milani S, Okolicsanyi L, Palasciano G, Portincasa P, Saltarelli P, Smedile A, Somalvico F, Spadaro A, Sporea I, Sorrentino P, Vecchione R, Tuccillo C, Del Vecchio Blanco C, Federico A. Silybin combined with phosphatidylcholine and vitamin E in patients with nonalcoholic fatty liver disease: a randomized controlled trial. Free Radic Biol Med. 2012 May 1;52(9):1658–65.
6. Aller R, Izaola O, Gómez S, Tafur C, González G, Berroa E, Mora N, González JM, de Luis DA. Effect of silymarin plus vitamin E in patients with non-alcoholic fatty liver disease. A randomized clinical pilot study. Eur Rev Med Pharmacol Sci. 2015 Aug;19(16):3118–24.
7. Sesti G, Fiorentino TV, Hribal ML, Sciacqua A, Perticone F. Association of hepatic insulin resistance indexes to nonalcoholic fatty liver disease and related biomarkers. Nutr Metab Cardiovasc Dis. 2013 Dec;23(12):1182–7.
8. Kawano Y, Cohen DE. Mechanisms of hepatic triglyceride accumulation in non-alcoholic fatty liver disease. J Gastroenterol. 2013 Apr;48(4):434–41.
9. Geisler CE, Renquist BJ. Hepatic lipid accumulation: cause and consequence of dysregulated glucoregulatory hormones. J Endocrinol. 2017 Jul;234(1):R1–R21.
10. Surapaneni KM, Vishnu Priya V, Mallika J. Effect of pioglitazone, quercetin, and hydroxy citric acid on vascular endothelial growth factor messenger RNA (VEGF mRNA) expression in experimentally induced nonalcoholic steatohepatitis (NASH). Turk J Med Sci. 2015;45(3):542–6.
11. Surapaneni KM, Jainu M. Pioglitazone, quercetin and hydroxy citric acid effect on hepatic biomarkers in Non Alcoholic Steatohepatitis. Pharmacognosy Res. 2014 Apr;6(2):153–62.
12. Scribner KB, Pawlak DB, Ludwig DS. Hepatic steatosis and increased adiposity in mice consuming rapidly vs. slowly absorbed carbohydrate. Obesity (Silver Spring). 2007 Sep;15(9):2190–9.
13. Ter Horst KW, Schene MR, Holman R, Romijn JA, Serlie MJ. Effect of fructose consumption on insulin sensitivity in nondiabetic subjects: a systematic review and meta-analysis of diet-intervention trials. Am J Clin Nutr. 2016 Dec;104(6):1562–76.
14. Softic S, Cohen DE, Kahn CR. Role of Dietary Fructose and Hepatic De Novo Lipogenesis in Fatty Liver Disease. Dig Dis Sci. 2016 May;61(5):1282–93.
15. Lim JS, Mietus-Snyder M, Valente A, Schwarz JM, Lustig RH. The role of fructose in the pathogenesis of NAFLD and the metabolic syndrome. Nat Rev Gastroenterol Hepatol. 2010 May;7(5):251–64.
16. Lonardo A, Ballestri S, Marchesini G, Angulo P, Loria P. Nonalcoholic fatty liver disease: a precursor of the metabolic syndrome. Dig Liver Dis. 2015 Mar;47(3):181–90.
17. Bremer AA, Mietus-Snyder M, Lustig RH. Toward a unifying hypothesis of metabolic syndrome. Pediatrics. 2012 Mar;129(3):557–70.
18. Martínez Steele E, Baraldi LG, Louzada ML, Moubarac JC, Mozaffarian D, Monteiro CA. Ultra-processed foods and added sugars in the US diet: evidence from a nationally representative cross-sectional study. BMJ Open. 2016 Mar 9;6(3):e009892.
19. Monteiro CA, Moubarac JC, Levy RB, Canella DS, Louzada MLDC, Cannon G. Household availability of ultra-processed foods and obesity in nineteen European countries. Public Health Nutr. 2017 Jul 17:1–9.
20. Moreira PV, Baraldi LG, Moubarac JC, Monteiro CA, Newton A, Capewell S, O’Flaherty M. Comparing different policy scenarios to reduce the consumption of ultra-processed foods in UK: impact on cardiovascular disease mortality using a modelling approach. PLoS One. 2015 Feb 13;10(2):e0118353.
21. Henry CJ, Kaur B, Quek RYC, Camps SG. A Low Glycaemic Index Diet Incorporating Isomaltulose Is Associated with Lower Glycaemic Response and Variability, and Promotes Fat Oxidation in Asians. Nutrients. 2017 May 9;9(5).
22. Bennett CB, Chilibeck PD, Barss T, Vatanparast H, Vandenberg A, Zello GA. Metabolism and performance during extended high-intensity intermittent exercise after consumption of low- and high-glycaemic index pre-exercise meals. Br J Nutr. 2012 Aug;108 Suppl 1:S8–90.
23. Singleton MJ, Heiser C, Jamesen K, Mattes RD. Sweetener augmentation of serum triacylglycerol during a fat challenge test in humans. J Am Coll Nutr 1999 Apr;18(2):179–85.
24. Tittelbach TJ, Mattes RD, Gretebeck RJ. Post-exercise substrate utilization after a high glucose vs. high fructose meal during negative energy balance in the obese. Obes Res 2000 Oct;8(7):496–505.
25. Poppitt SD, Keogh GF, Prentice AM, Williams DE, Sonnemans HM, Valk EE, Robinson E, Wareham NJ. Long-term effects of ad libitum low-fat, high-carbohydrate diets on body weight and serum lipids in overweight subjects with metabolic syndrome. Am J Clin Nutr. 2002 Jan;75(1):11–20.

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Commonly over the long term in type 2 diabetes mellitus, insulin resistances increases blood glucose levels followed by a compensatory rise in circulating insulin concentrations with the latter being the body’s attempt to adapt to the former. Consequences include high blood sugar levels, prolonged high insulin levels, the appearance of medical complications and the exhaustion of the pancreas’ ability to produce insulin.

The core of the metabolic syndrome thus is the dysregulation and dysfunction involving glucose and insulin. Aside from these, secondary characteristics encompass central obesity, hypertension, and dyslipidemias—especially hypertriglyceridemia and low levels of HDL cholesterol. In addition to participating in the development of many facets of the metabolic syndrome, impairment in insulin sensitivity also appears to be involved in the aging process by promoting inflammation, endothelial dysfunction, the production of advanced glycation end products (AGE), and oxidative stress. Downstream consequences of these dysfunctions include cardiovascular disease and cancer.

Several major questions have emerged regarding the appearance of the metabolic syndrome. Western medicine, unlike, for instance, traditional Chinese and Indian medicine, tends to pursue and treat the various arms of the metabolic syndrome as distinct clinical entities. Much of the research on the syndrome within allopathic medicine over the past three decades has been aimed at arguing against this separation. Another issue is the level of insulin resistance that should be taken as requiring attention. Most clinicians consider a level of circulating glucose under fasting conditions in the range of 100–125 mg/dl to be pre-diabetic. And then there is the issue of inevitability, which is to say, does the metabolic syndrome arise as a consequence of aging?

Early Signs of the Metabolic Syndrome in Non-Diabetics

For some time, there have been questions as to what should be acceptable as a normal fasting glucose level. Circulating glucose within levels generally accepted as normal can influence brain function in an unfavorable manner and increasing hemoglobin AlC (HbAlC) and insulin levels even in the non-diabetic range may affect blood pressure adversely. Such observations lead to suspicions that minor insulin resistance predicts the early onset of many disturbed health parameters involved in the metabolic syndrome. Recently Harry G. Preuss and co-authors, of whom I am one, addressed just such questions in “Fasting Circulating Glucose Levels in the Non-Diabetic Range Correlate Appropriately with Many Components of the Metabolic Syndrome.” ¹ Those with special interests should consult that journal and a forthcoming more detailed article.

To be sure, despite access to a large number of medical records, our study faced technical limitations. Because we worked exclusively with subjects possessing non-diabetic fasting glucose concentrations, the other measured clinical values, for the most part, fell in the accepted normal range. Therefore, correlations rather than exact numbers were largely used to determine alterations in health modalities. For corroboration, however, we examined statistical differences in the various parameters between the highest and lowest quartiles associated with these fasting glucose levels. Our data in this preliminary study are representative of the general population in middle and late middle age. The hypothesis is that glucose/insulin perturbations are at the heart of the increased incidence and severity of the various constituents making up the metabolic syndrome and could hasten/ worsen the aging process. A major goal in the study was to cast light on the issue of whether aging itself is associated with the development of the components of the metabolic syndrome or whether, to the contrary, containment of fasting insulin/glucose levels to a relatively low level reduced the appearance of the metabolic syndrome components despite advancing age.

Findings
Despite the fact that the population sample consisted entirely of individuals with fasting blood glucose readings below those of diabetes, there was a clear positive correlation between rising glucose levels and metabolic syndrome components. As expected, the average, baseline values of most parameters were in the accepted normal range. Nevertheless all of the following increased more or less in tandem with rising glucose levels: body weight, body fat mass, systolic/diastolic BP, HbA1C, circulating levels of insulin, triglycerides, hsCRP (highly sensitive C-reactive protein) and along with a number of other components representing inflammation and liver health. Elevated non-diabetic glucose levels were associated with signs of augmented inflammation (increased hsCRP, white cell and neutrophil cell counts) and liver perturbations (increased ALT) proposed to play a role in the metabolic syndrome.

On the reverse side, high-density lipoprotein (HDL) showed a negative correlation, meaning that higher blood glucose levels lead to lower HDL levels. Put another way, unlike fasting glucose, when total cholesterol became the independent variable, the majority of these health parameters improved showing beneficial correlations compared to fasting glucose. However, when examining the total cholesterol minus HDL-cholesterol correlations, all benefits of total cholesterol are lost, suggesting that the benefits noted with total cholesterol are primarily due to the presence of HDL-cholesterol.

We concluded that the early onset of the various risk factors correlating with circulating fasting glucose suggests a significant role for insulin resistance in the development of the metabolic syndrome. HbA1C and insulin values are also be linked to insulin resistance, but we chose to follow a more common, clinically available marker—circulating fasting glucose levels. Fasting glucose concentrations and the levels of HbA1C and insulin are significantly correlated, therefore findings are similar whether one tests using fasting glucose levels or insulin levels.

What is the ideal range of fasting blood glucose? Based on our preliminary study, the health data were significantly better with glucose levels in the range of 67–86 mg/dL than at 98–125 mg/dL. Across a wide range of variables, lower definitely was better. Another finding, one only touched on in the provisional version of the study described here, is that aside from blood pressure, age did not seem to play a significant independent role in determining metabolic syndrome health risks and even with regard to increasing systolic blood pressure (the top figure) the influence was less than expected. Glucose and insulin levels were the primary drivers of risk factors, not age.

Conclusion
If glucose and insulin levels are the primary sources of metabolic syndrome risks, then enhancing insulin sensitivity and lowering circulating glucose levels are steps that should be taken to promote and maintain health. Fortunately, many of the means to encourage better glucose control are relatively easy. Diet no doubt is key. Sugar, refined carbohydrates and excessive calorie consumption definitely are not friends of good health. Neither are bad eating habits, which include skipping breakfast, eating late in the day and snacking, especially at bedtime. Exercise can be very helpful, particularly taking at least a 15-minute brisk walk before lunch and again later in the day. All of these measures amount to the ounce of prevention advice that actually does work, but only so long as it is followed!

References:

1. Preuss, H. G., Clouatre, D, et al. Fasting Circulating Glucose Levels in the Non-Diabetic Range Correlate
2. Appropriately with Many Components of the Metabolic Syndrome. The Original Internist June 1, 2016, pp. 78ff.

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There are other reasons cooking can be both friend and foe of nutrition. Over-cooking can destroy nutrients because of heat and oxidation, cause them to be tossed out with cooking water, and so forth. In contrast, cooking can make available compounds that otherwise digestion normally cannot extract from raw food. In this particular case, it was found that frying in extra virgin olive oil transferred to vegetables polyphenols from the oil and thereby improved the antioxidant capacity of the vegetables in comparison with either raw or boiled alternatives. The particular new healthful polyphenols were shown to be from the oil and not found originally in the raw vegetables. The further implication is that frying in oils of lesser quality will lead to vegetables that are not as nutritious as those fried in extra virgin olive oil.

Frying with Extra Virgin Olive Oil for Extra Nutrition
Nutrients in raw vegetables often are less bioavailable than is true when the same vegetables are cooked. Likewise, cooking sometimes leads to beneficial transformations of nutrients. The degree to which these claims are true varies from vegetable-to- vegetable and with the cooking method employed. In the present study in Food Chemistry, potato, tomato, eggplant and pumpkin (120 grams each) were deep fried, sautéed and boiled. Extra virgin olive oil was used for the frying and also added to cooking water to create a water/oil mixture; the third cooked arm employed water only. The methods used were typical of standard cooking techniques. Deep fat frying used five parts oil to one part vegetable, whereas sautéing used one half as much oil as vegetable; temperatures were approximately 360 °F and 175–212 °F, respectively. Boiling used five parts water or five parts water/oil to one part vegetable. Cooking lasted 10 minutes; vegetables were drained for an additional five minutes and then refrigerated before being homogenized for testing.

Testing before and after cooking determined fat, moisture, total phenols (or phenolics, referring to the chemical structure of these nutrients), eighteen phenolic compounds and antioxidant capacity. Not surprisingly, deep-frying led to the greatest moisture loss and the greatest gain in fat; sautéing increased fat content less without appreciably changing the moisture content versus the raw state. Depending on the vegetable, boiling either increased moisture or exercised no significant effect; boiling in the water/oil mixture increased vegetable oil content.

Changes in phenolic nutrients were more complex. Deep-frying increased these significantly for all four vegetables by reducing moisture. Sautéing led to nutrient increases in potato and pumpkin, but only non-significant increases in eggplant and tomato. For eggplant, sautéing reduced total endogenous phenolics, primarily chlorgenic acid, apparently because of oxidation from exposure to air due to not being totally covered by the oil. Total phenolics fell in both potato and pumpkin from either method of boiling. Both frying techniques increased phenolic nutrients typical of extra virgin oil indicating a transfer to the vegetables of oleuropein, pinoresinol, hydroxytyrosol, tyrosol, p-coumaric acid and hydroxybenzoic acid. Phenolic nutrients already found in these vegetables, such as chlorogenic acid and rutin, increased except in the eggplant. Interestingly, all the cooking methods conserved or increased antioxidant capacity in the order of deep-frying, sautéing, and then boiling. The best results with either form of boiling required that the cooking water be consumed along with the vegetable.

About that Olive Oil…
Extra virgin olive oil is oil that has undergone the least processing and that retains the highest levels of naturally occurring polyphenols. Extra virgin and virgin olive oils are good sources of antioxidants and other healthful compounds.

The study in Food Chemistry shows that not all of these healthful compounds are lost in cooking, not even in relatively high-temperature deep-frying. Instead, significant amounts can be transferred to the food being cooked. This is an important finding, in part because it extends the range of uses of olive oil beyond, for example, dressings for salads, and also because it indicates that olive oil is important for more than simply being a source of monounsaturated fatty acids. A quick look at research publications limited even to just 2015 yields papers showing that olive oil polyphenols.

• Inhibit oxidative damage to lipoproteins, including LDL cholesterol, and at the same time improve the functionality of HDL-cholesterol, including the cholesterol efflux capacity to pick up excess cholesterol from peripheral tissues and return it to the liver for disposal
• Helps to lower blood pressure in both men and women
• Improves the physiology of the endothelium, a type of cell that lines the interior surface of blood and lymph vessels
• As part of the Mediterranean diet, exercise favorable effects on a large range of cardiovascular risk factors

Foods: Raw or Cooked?
As with many such debates, evidence for the raw versus cooked food dispute does not neatly come down to either/ or choices. Are some nutrients damaged or otherwise lost during cooking? Yes, some are. However, as the study above shows, depending on the food, nutrients can become more concentrated and cooking itself can add nutrients. Digestive enzymes are not particularly good at breaking the cell walls found in many vegetables. In these cases, cooking makes much more bioavailable many nutrients. The carotenoids from carrots are good examples of this phenomenon. Again, the lycopene in tomatoes is three or more times more bioavailable from cooked tomatoes, especially when cooked with oil, than from raw tomatoes. Small changes in cooking technique, such as not cooking vegetables in large volumes of water and then tossing the cooking water, can save many vitamins, minerals and other nutrients. A judicious balance of raw and properly cooked foods is more likely to yield a full range of healthful nutrients than is either approach alone.

Endnote:

1. Ramirez-Anaya Jdel P, Samaniego-Sanchez C, Castaneda-Saucedo MC, Villalon-Mir M, et al. Phenols and the antioxidant capacity of Mediterranean vegetables prepared with extra virgin olive oil using different domestic cooking techniques. Food Chem. 2015 Dec 1;188:430—8.

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The causes of depression and mood disorders remain an area of controversy. Human beings are prepared to react to vastly varied environmental factors. Not surprisingly, many biological and psychological factors cut in more than one direction. Metabolic factors (inflammation, insulin resistance, and oxidative stress) are not necessarily one-direction in terms of causation, for example, with regard to emotional and physical stress and the resulting stress hormones (glucocorticoids). Sex hormones (testosterone, estrogen), likewise, both influence and are influenced by emotional and physical factors.

Is Inflammation the Central Issue?
The concept of inflammation in the last few years has been stretched to cover more and more forms of illness and dysfunction. One reason is that inflammation is actually a set of responses that occur naturally all the time, yet each of which can itself escape proper regulation. You get a sense of this from the article on inflammation available online from Wikipedia: “Inflammation is a protective response that involves immune cells, blood vessels, and molecular mediators. The purpose of inflammation is to eliminate the initial cause of cell injury, clear out necrotic cells and tissues damaged from the original insult and the inflammatory process, and to initiate tissue repair.” Inflammation thus involves both destruction and repair.

A number of researchers are looking into the issue of neuroinflammation outside of the traditional medical areas of concern, such as stroke. For instance, psychological stress has been demonstrated to increase neuroinflammation in animal models.⁴ Similarly, there is evidence to support the position that links chronic depression to chronic brain inflammation and acute depression to stress-triggered neuronal microdamage.⁵ Another line of argument is that the “metabolic syndrome and its individual components induce a pro-inflammatory state that damages blood vessels. This condition of chronic inflammation may damage the vasculature of the brain or be directly neurotoxic.”⁶

Countering Depression without Drugs
Inflammation and the metabolic syndrome are closely linked in physiology and biochemistry. Therefore, it should not come as a surprise that studies on obesity, diet and exercise habits often turn up implications for preventing and treating depression. For example, a large study of 15,093 people published in 2015 indicated that depression could be linked with nutrient deficits. The best results were found with two essentially Mediterranean-style diets. These diets overlapped in terms of foods such as omega-3 fatty acids, vegetables, fruits, legumes, nuts and moderate alcohol intake. Another finding was that there apparently is a threshold effect, meaning that a certain level of protective foods needed to be in the diet, but that benefits in terms of reduced risk of depression plateaued after this threshold was passed.⁷

It is difficult to find many nutrients that can be given as dietary supplements that cross the blood-brain barrier. Many of the nutrients that are of use are from berries. Pterostilbene, but not resveratrol, is a potent neuromodulator in aging and Alzheimer’s disease.⁸ “Blueberry, strawberry, blackberry, grape and plum juices or extracts have been successfully tested in cognitively impaired rodents. Published trials of the benefits of grape and blueberry juice in the treatment of small numbers of cognitively impaired persons have recently appeared.”⁹ Another potentially useful item in this regard is the Chinese herb known as blue dogbane, Apocynum venetum. This interesting item, virtually unknown outside of Asia, exerts proven anti-depressant effects, in part, via brain monoamine levels and the dopaminergic system. The latter, again, is influenced by pterostilbene, but not resveratrol.¹⁰ Of importance regarding the impact of Apocynum venetum on inflammation is its high content of the potent antioxidant / anti-inflammatory, isoquercitrin.¹¹

A complementary option to the foregoing nutrients is to reduce the impact of stress. Phosphatidylserine (PS) supports the brain’s physiological processing of stress and promotes neuronal communication by its effect on cell membrane fluidity. It is a natural phospholipid that is an essential component of cell membranes. PS promotes brain function by increasing neuronal membrane fluidity (cell-to-cell communication), resulting in improved cognition. Also, PS protects against stress by mitigating the actions of cortisol (catabolic stress hormone.) Human research routinely demonstrates these benefits and suggests the usefulness of a combination with DHA, e.g., “The results demonstrate that consumption of 100 mg/day of PS-DHA might be associated with improving or maintaining cognitive status in elderly subjects with memory complaints.”¹²

Finally, there is the issue of the relation between Alzheimer’s and sugar consumption. In old age, there tends to be an increasingly significant association between forms of cognitive impairment and depression. Some believe there’s a connection between sugar intake and Alzheimer’s disease. There are a number of theories as to why this might be. One argument is that increased consumption of simple carbohydrates leads to blood brain barrier degradation and subsequently to damage to the hippocampus.¹³ A related argument is that increased consumption of simple carbohydrates leads to elevations of specific advanced glycation end products (AGEs), especially the neurotoxic methyl-glyoxal derivatives (MG). High levels of AGEs also are correlated with reduced insulin sensitivity in older human adults. These factors promote chronic oxidant stress and inflammation in the brain.¹⁴

Endnotes:

1. Lavretsky H, Alstein LL, Olmstead RE, Ercoli LM, Riparetti-Brown M, Cyr NS, Irwin MR. Complementary use of tai chi chih augments escitalopram treatment of geriatric depression: a randomized controlled trial. Am J Geriatr Psychiatry. 2011 Oct;19(10):839–50.
2. Gartlehner G, Gaynes BN, Amick HR, Asher G, Morgan LC, Coker- Schwimmer E, Forneris C, Boland E, Lux LJ, Gaylord S, Bann C, Pierl CB, Lohr KN. Nonpharmacological Versus Pharmacological Treatments for Adult Patients With Major Depressive Disorder [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2015 Dec.
3. Gartlehner G, Gaynes BN, Amick HR, Asher GN, Morgan LC, Coker- Schwimmer E, Forneris C, Boland E, Lux LJ, Gaylord S, Bann C, Pierl CB, Lohr KN. Comparative Benefits and Harms of Antidepressants, Psychological, Complementary, and Exercise Treatments for Major Depression: An Evidence Report for a Clinical Practice Guideline From the American College of Physicians. Ann Intern Med. 2016 Feb 9. [Epub ahead of print]
4. Barnum CJ, Pace TW, Hu F, Neigh GN, Tansey MG. Psychological stress in adolescent and adult mice increases neuroinflammation and attenuates the response to LPS challenge. J Neuroinflammation. 2012 Jan 16;9:9.
5. Wager-Smith K, Markou A. Depression: a repair response to stress-induced neuronal microdamage that can grade into a chronic neuroinflammatory condition? Neurosci Biobehav Rev. 2011 Jan;35(3):742–64.
6. Cherniack EP. A berry thought-provoking idea: the potential role of plant polyphenols in the treatment of age-related cognitive disorders. Br J Nutr. 2012 Sep;108(5):794–800.
7. Sánchez-Villegas A, Henríquez-Sánchez P, Ruiz-Canela M, Lahortiga F, Molero P, Toledo E, Martínez-González MA. A longitudinal analysis of diet quality scores and the risk of incident depression in the SUN Project. BMC Med. 2015 Sep 17;13:197.
8. Chang J, Rimando A, Pallas M, Camins A, Porquet D, Reeves J, Shukitt- Hale B, Smith MA, Joseph JA, Casadesus G. Low-dose pterostilbene, but not resveratrol, is a potent neuromodulator in aging and Alzheimer’s disease. Neurobiol Aging. 2012 Sep;33(9):2062–71.
9. Cherniack EP. A berry thought-provoking idea: the potential role of plant polyphenols in the treatment of age-related cognitive disorders. Br J Nutr. 2012 Sep;108(5):794–800.
10. Zheng M, Fan Y, Shi D, Liu C. Antidepressant-like effect of flavonoids extracted from Apocynum venetum leaves on brain monoamine levels and dopaminergic system. J Ethnopharmacol. 2013 May 2;147(1):108–13.
11. Butterweck V, Nishibe S, Sasaki T, Uchida M. Antidepressant effects of apocynum venetum leaves in a forced swimming test. Biol Pharm Bull. 2001 Jul;24(7):848–51.
12. Vakhapova V, Cohen T, Richter Y, Herzog Y, Kam Y, Korczyn AD. Phosphatidylserine containing omega-3 Fatty acids may improve memory abilities in nondemented elderly individuals with memory complaints: results from an open-label extension study. Dement Geriatr Cogn Disord. 2014;38(1–2):39–45.
13. Hsu TM, Kanoski SE. Blood-brain barrier disruption: mechanistic links between Western diet consumption and dementia. Front Aging Neurosci. 2014 May 9;6:88.
14. Cai W, Uribarri J, Zhu L, Chen X, Swamy S, Zhao Z, Grosjean F, Simonaro C, Kuchel GA, Schnaider-Beeri M, Woodward M, Striker GE, Vlassara H. Oral glycotoxins are a modifiable cause of dementia and the metabolic syndrome in mice and humans. Proc Natl Acad Sci U S A. 2014 Apr 1;111(13):4940–5.

The post Depression, Inflammation, and Nutrition appeared first on Total Health Magazine.

SYNERGY
Synergism—the combined effects of two or more components is greater than the sum of the effects of the individual components acting alone

Many years ago, I was involved in the development of patentable forms of grape seed extract and their proanthocyanidin active components. We were exploring, among other things, how plant compounds work together with traditional antioxidant vitamins to provide protection that is superior to that of vitamins alone. People whose diet is rich in fruits and vegetables consume not only antioxidant vitamins, but also various polyphenols. Our starting point was that many of the benefits derived from eating such diets may be the result of synergism between the plant polyphenols and the better-known vitamin antioxidants. Plant polyphenols in this consideration were active antioxidant compounds, such as those found in tea, wine and grape juice. Overwhelming evidence supports the belief that excessive oxidation and free radical damage is linked to various disease states and even to aging. Yet studies in both animals and humans in which diets have been supplemented with antioxidant vitamins for long periods of time have yielded ambiguous results.

At the 219th American Chemical Society National Meeting held in San Francisco on March 26–30, 2000 researchers associated with the company Polyphenolics presented studies that supported supplementing the diet with special plant-derived nutrients and consuming more whole fruits and vegetables. One of our associates pointed out that antioxidant vitamins are present in the human body at levels typically twenty to several hundred times the level of plant polyphenols. This is one reason that so much less research has focused on the antioxidant vitamins in foods and relatively little research has been done on the antioxidant roles of the other compounds present. By 2000, however, it already was becoming clear that these non-vitamin plant antioxidants have an impact on the antioxidant status of the body that is much beyond their representation in the blood and tissues. For instance, at the conference it was explained that an extract from grape seeds given to human volunteers led to a much greater increase in the antioxidant capacity of the subjects’ blood than was theoretically possible based on the compound alone. This was a finding that called for explanation. A second set of tests helped to clarify the result of the first––the same grape seed extract demonstrated significant synergism when tested in vitro with the antioxidant vitamins C and E, either alone or in combination.

To establish a quantitative baseline for the antioxidant power of each of the compounds, tests used the standard cupric ion generation of oxidation to look at the impact of combining our grape seed extract (Vixox Gold™) with vitamins C and E to gauge the synergy of the combinations. Vitamin C, vitamin E and grape seed extract were each tested individually to determine their effects at several concentrations. These baselines were added to yield the “Sum of Individual Inhibitions” which then was compared with the “Actual Inhibitions When Tested Together.” The Actual Inhibitions minus the Sum of Individual Inhibitions times 100 yielded the percent of Synergism. This series of in vitro tests thus allowed the investigator to elegantly demonstrate the concentrations of maximal synergism amongst the three antioxidants. Strong synergism was shown for Vinox Gold™ plus vitamin C, for Vinox Gold™ plus vitamin E, and, finally, for Vinox Gold™ plus vitamin C and vitamin E.

Synergisms in the ranges shown above are good examples of why it is that consuming a diet rich in fruit and vegetables is so much more successful in terms of health than eating a diet based on refined carbohydrates, protein and fats. Refining the “big three” macronutrients and then “adding back” nutrients/ micronutrients loses the benefits of the plant compounds that otherwise are present in the original sources of carbohydrates and in partially refined oils, such as olive and sesame oils. The antioxidant vitamins are important, but they commonly provide their full potential benefits only when combined with various plant factors.

BEYOND SYNERGISM
Synergism is important, yet there are other arguably much more important factors that cannot be reduced to the concept of synergism. In another paper presented at the American Chemical Society National Meeting, Chithan Kandaswami of the State University of New York at Buffalo indicated that grape seed extract acts in ways other than as an antioxidant. The flavonoids found in grape seed along with chemically similar compounds found in other plants act to reduce the signals received by certain cell receptors involved in inflammation and tumor growth and to activate additional signals. Antioxidants commonly are found to help to reduce inflammation, but in this case the protective effect is different from an antioxidant benefit. When researchers attempt to elucidate mechanisms of action, compounds found in foods and herbs often exhibit signaling roles in the body with difficult to define effects and unknown active pathways.

To illustrate this, let’s take a simple example with implications that upend many supposedly established conclusions and vast amounts of research into the relation between nutrition and cardiovascular disease. Saturated fats, such as butterfat, long have been damned based mostly on marker studies as being atherogenic because such fats raise plasma total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C). In 2015, it has become apparent that recommendations against saturated fats that have been in place since 1977 never had conclusive support from randomized controlled trials and that there is a case to be made that total cholesterol and, to some extent, even LDL-C, within a wide range actually are inversely related to total mortality! ^1,2,3,4,5 This means that longevity studies based on endpoints (did the subjects live longer or not) routinely have found that in old age higher, not lower, levels of total and even LDL-C within a certain range are associated with better health and longer life. The reader may well ask, “How can so much have been wrong for so long?” One answer is that models based on interventions with pure substances often leave out actual dietary practices and suggest that foods which, in fact, are healthful instead are detrimental to health. Case in point, butterfat.

In 1993, one of the most important researchers exploring the health effects of fats in the diet, FA Kummerow, published an animal study using a model (swine) that is an almost perfect stand-in for humans in terms of lipids and cardiovascular disease to test the effects of consumption of margarine and butter on plasma lipids levels as different amounts of magnesium were consumed. The findings were telling regarding nutrient interactions. From the abstract:

Plasma lipids obtained from swine which had been fed butter or margarine at two dietary magnesium (Mg) levels indicated that the level of dietary Mg was more significant to plasma total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels than was the presence of butter or margarine [i.e., omega-6 polyunsaturated fatty acids].…

Studies in which the influences of dietary fats on plasma cholesterol were first noted were carried out on liquid diets deficient in Mg. Mg, a cofactor in the enzymes involved in desaturation of saturated fatty acids, is also necessary in desaturation of linoleic to arachidonic acid.

⁶ [Emphasis added.]

In other words, simply adding magnesium to the diet dramatically changed the effect of saturated fat on plasma lipids levels compared to polyunsaturated fat. Interestingly, butterfat, such as is found in full fat dairy, actually protects against diabetes and perhaps other components of the metabolic syndrome.⁷ The addition of magnesium in this example is not a form of synergy in the usual sense defined above. Instead, it is an instance of how in the diet the entourage effect often plays out.

THE ENTOURAGE EFFECT
Many herbalists long have held that in some cases plants yield better results than the natural products isolated from them, a type of “herbal synergism.” However, synergy in the simple sense introduced above involves the total of a particular benefit or effect being greater than the sum of its parts. This is illustrated by the example of delivering together blends of antioxidants whose antioxidant effects, through whatever combination of mechanisms, exceed the sum of their individual capacities as antioxidants. But what do we call the concept if one or more of the components exert no antioxidant effects of their own, may otherwise seemingly even be inert, yet magnify the outcome, reduce side effects and introduce new and unexpected benefits?

Increasingly in the scientific literature, this is called the entourage effect.⁸ Not surprisingly, the concept emerged with regard to herbs rather than standard pharmaceuticals because it does not lend itself readily to standard testing methodologies which depend upon “one cause, one effect” reasoning and testing. Nevertheless, examples of the entourage effect continuously are in evidence.

A good illustration of the superiority of a complex herbal extract versus “guaranteed potency” based on the ever greater purification of a single ingredient is Ma huang, a plant source of natural ephedra. Starting in the early 1990s and continuing for more than a dozen years, the combination of ephedra and caffeine was popular as a dieting aid because the mixture worked. Despite this fact, ephedra and its sources were banned due to fears of increased hypertension in vulnerable individuals. In the marketplace, relatively high dose extracts from plant sources were not economic beyond concentrations of six percent of the active alkaloid and this led to the widespread use of synthetic sources. Curiously, seriously elevated blood pressure was not normal with the plant source at reasonable levels of intake whereas elevated blood pressure was fairly typical with the synthetic. Why the difference? The answer lay with the entourage effect—in Ma huang there are a number of compounds that lower blood pressure and otherwise modulate the pressor effect of ephedra thus making the plant source far safer than the synthetic pharmaceutical source of ephedra.

Similar cases are found throughout herbalism. The important compound adenosine cannot be successfully supplemented in pure form by mouth, yet is bioavailable as a component of bears’/wild garlic.⁹ Likewise, the phytosterols beta-sitosterol and its glucoside in combination show significantly greater efficacy than the individual sterols at the same concentration, which is to say beta-sitosterol requires the presence of its typical form found in plants in order to be maximally active.¹⁰

A great current example of the entourage effect is cannabis in both its medical and recreational uses. Different strains of the plant that otherwise are analyzed as possessing essentially identical amounts of the “active” ingredients are reported by many or even most users as leading to quite different experiences. The reason is that the plant is the source of 60 or more cannabinoids alone, not just the famous THC and CBD, along with a host of non-cannabinoid compounds, such as terpenes. These differing combinations of compounds can activate or block binding to brain receptor sites and produce a variety of other regulatory effects.

These findings have wide-ranging implications, such as for the use of medical marijuana for cancer. For instance, cannabinoids typically have been used in experimental treatments just like other drugs to block one or another pathway or receptor site based on the genetic mutation theory of tumor development and growth. However, that model, which is the basis of most chemo- and related therapies, recently has taken quite a few hard nocks as it has become increasing apparent that cancers, like other cells and tissues in the body, depend upon epigenetics as much as or more than genetics.^11,12

Epigenetics, according to one definition, refers to external modifications to DNA that turn genes “on” or “off.” These modifications do not change the DNA sequence, but instead, they affect how cells “read” genes.¹³

In epigenetic models of disease, targeting multiple pathways and influencing indirect as well as direct mechanisms is more effective than focusing on a single point.

A PRINCIPLE IN TRADITIONAL HERBAL FORMULATION

The entourage effect as a concept very recently has been harnessed by scientists at Harvard and several Central European universities to cover ways of visualizing the relationships between biological pathways.¹⁴An argument can be made a number of sophisticated traditional medical systems, such as those of the Tibetans and the Chinese, long have employed this type of modeling. Indeed, neither of these systems nor the related Indian Ayurvedic system traditionally used single herbs in treatments. As one recent compendium describes the principles of Traditional Chinese Medicine:

Chinese herbs are not used singly in treatment, but in combinations known as herbal formulas….Since a [sic] herbal combination has obvious advantages in treatment, the relationships between the herbs used in traditional Chinese medicine (TCM) have been carefully studied and certain types of relationship are identified. They are called the seven relations between herbs, e.g. mutual accentuation, mutual enhancement, mutual counteraction, mutual suppression, mutual antagonism, mutual incompatibility and single effect. Some of these are very useful in treatment, but some are harmful and therefore must be avoided.¹⁵

There are other ways of describing principles of formulation, such as major ingredients, directing ingredients, various modifying ingredients, etc., but the ideas are similar.

To illustrate these points, we can return to a Chinese formula that has been mentioned before in these pages, the fermented herb mixture known as Tai Li Wang. Also referred to as a mulberry and sea-buckthorn beverage concentrate to reflect its two most prominent ingredients, Tai Li Wang is suggested for individuals under stress, including mental and physical stress, those recovering from surgery or illness, requiring a large nutritional boost, individuals suffering gastrointestinal problems, and those looking for an anti-aging tonic. Other ingredients include black sesame, black plum, goji, Buddha’s hand, Chinese white olive, fu ling, chrysanthemum and jujube. Fermentation creates further complex components not found in the original herbs. The herbal tradition maintains that Tai Li Wang improves energy, supports the liver and kidney functions, increases blood components and supports their roles, is detoxifying, improves digestion and digestive functions (including being useful in both constipation and diarrhea), and is calming, including aiding sleep. In short, the formula is strengthening and balancing to the metabolism.

These effects refer to the entire formula and the components individually are generally mild in action. However, even mild herbs have limits. Take, for instance, Buddha’s hand. This is a mild herb related to citron that calms the liver and regulates certain types of energy. It is not used by itself if the physiologic system has been depleted due to diarrhea. Similarly, chrysanthemum typically is mild with the properties of cooling and calming, yet it should be used in moderation by those who have a weak digestive system or have diarrhea. The other herbs in the formula balance these constraints and in practice Tai Li Wang serves to normalize bowel function just as it serves to support immune function without causing inflammation and it promotes greater energy without being overly stimulating or depleting as is caffeine. In general, Tai Li Wang is a complex mixture of herbs consumed at really quite low levels as individual components, meaning that its benefits cannot be explained by the quantity of any one component, yet taken together these ingredients magnify the outcome, reduce side effects and introduce new and unexpected benefits.

CONCLUSION
As noted above, herbalists long have held that in some cases plants yield better results than the natural products isolated from them, a type of “herbal synergism.” One of the dangers of the modern “guaranteed potency herbs” and similar approaches to supplements is that the “guaranteed potency” that originally was meant to insure that the whole extraction was done properly has been deformed to reproduce the pharmaceutical model of pure substances and, as one consequence, leaving out important compounds found in the herbs and in the extracts as originally produced. Single compound and herbs can be combined for synergistic effects, to be sure, but it is easy to lose sight of the benefits, sometimes not at all minor, of the other compounds present in the herbs that may not constitute the active ingredients per se, yet are important for determining how the so-called active ingredients affect the body. This is the entourage effect. It is important in evaluating individual herbs and their extracts. Properly understood, it also can be understood as an organizing principle for a number of traditional medical systems, such as those of the Tibetans and the Chinese.

References

1. Harcombe Z, Baker JS, Cooper SM, Davies B, Sculthorpe N, DiNicolantonio JJ, Grace F. Evidence from randomised controlled trials did not support the introduction of dietary fat guidelines in 1977 and 1983: a systematic review and meta-analysis. Open Heart. 2015 Jan 29;2(1):e000196.
2. Hamazaki T, Okuyama H, Ogushi Y, Hama R. Towards a Paradigm Shift in Cholesterol Treatment. A Re-examination of the Cholesterol Issue in Japan. Ann Nutr Metab. 2015;66 Suppl 4:1-116. doi: 10.1159/000381654.
3. Ericson U, Hellstrand S, Brunkwall L, Schulz CA, Sonestedt E, Wallström P, Gullberg B, Wirfält E, Orho-Melander M. Food sources of fat may clarify the inconsistent role of dietary fat intake for incidence of type 2 diabetes. Am J Clin Nutr. 2015 May;101(5):1065–80.
4. de Souza RJ, Mente A, Maroleanu A, Cozma AI, Ha V, Kishibe T, Uleryk E, Budylowski P, Schünemann H, Beyene J, Anand SS. Intake of saturated and trans unsaturated fatty acids and risk of all cause mortality, cardiovascular disease, and type 2 diabetes: systematic review and meta-analysis of observational studies. BMJ. 2015 Aug 11;351:h3978.
5. Morowitz HJ. Hiding in the Hammond Report. Hospital Practice 1975 Aug:35,39.
6. Kummerow FA, Wasowicz E, Smith T, Yoss NL, Thiel J. Plasma lipid physical properties in swine fed margarine or butter in relation to dietary magnesium intake. J Am Coll Nutr. 1993 Apr;12(2):125–32.
7. Op cit. note 3.
8. Russo EB. Taming THC: potential cannabis synergy and phytocannabinoidterpenoid entourage effects. Br J Pharmacol. 2011 Aug;163(7):1344–64.
9. Preuss HG, Clouatre D, Mohamadi A, Jarrell ST. Wild garlic has a greater effect than regular garlic on blood pressure and blood chemistries of rats. Int Urol Nephrol. 2001;32(4):525–30.
10. Bouic PJ, Etsebeth S, Liebenberg RW, Albrecht CF, Pegel K, Van Jaarsveld PP. beta-Sitosterol and beta-sitosterol glucoside stimulate human peripheral blood lymphocyte proliferation: implications for their use as an immunomodulatory vitamin combination. Int J Immunopharmacol. 1996 Dec;18(12):693–700.
11. Rozhok AI, DeGregori J. Toward an evolutionary model of cancer: Considering the mechanisms that govern the fate of somatic mutations. Proc Natl Acad Sci USA. 2015 Jul 21;112(29):8914–21.
12. Epigenetics: A New Frontier in Cancer Research. AICR ScienceNow, Volume 20, Spring 2007 at http://preventcancer.aicr.org/site/News2?abbr=res_&id=11800
13. http://www.livescience.com/37703-epigenetics.html
14. Lex A, Partl C, Kalkofen D, Streit M, Gratzl S, Wassermann AM, Schmalstieg D, Pfister H. Entourage: visualizing relationships between biological pathways using contextual subsets. IEEE Trans Vis Comput Graph. 2013 Dec;19(12):2536–45.
15. Yifan Yang. “Theories and concepts in the composition of Chinese herbal formulas” in Chinese Herbal Formulas: Treatment Principles and Composition Strategies. (Edinburgh and New York: Churchill Livingstone Elsevier, 2010.)

The post Beyond Synergy The Entourage Effect in Nutrition & Herbalism appeared first on Total Health Magazine.

Traditional medical systems around the world are much more focused on convalescence from illness and injury. Broths and soups are at home in European traditions, of course. In Indian and Chinese culture these variously are enriched with special herbs and spices. For instance, the Ayurvedic tradition makes use of a rice and dahl (yellow lentil) dish called kicharee that is prepared fresh daily for convalescence. This meal can be quite varied, yet typically contains a little ghee, onions, garlic, ginger and a variety of mild warming and digestive herbs and spices, with vegetables added to taste and as the patient grows stronger. Chinese tradition suggests chicken and meat/bone broths, soups and stews along with certain herbs, such as wolfberry, angelica, ginger, jujube (a special date), and so forth. Indeed, in Chinese medicine tonification to match various conditions is a sophisticated science. (See, for instance, http://www.shen-nong.com/eng/lifestyles/tcmrole_bufa.html) A section below discusses a really quite remarkable representative of this tradition: tai li wang mulberry and sea-buckthorn beverage concentrate. This ancient formula addresses some of the key weaknesses experienced by individuals who have undergone chemotherapy, radiation and surgery.

Chemotherapy and Radiation: Why Is Recovery So Hard?

Chemotherapy and radiation are based in large part on the greater susceptibility of cancer cells to damage than is true of normal cells. Cancerous tissues have certain metabolic advantages over healthy tissues that allow them to grow faster and to cannibalize surrounding tissues to feed themselves. This sometimes is called the “Warburg effect” after the Nobel Prize winner who first described it. Cancer’s growth advantage comes with certain downsides, such as greater susceptibility to damage by free radicals and many toxins. Chemotherapy works in part by being more toxic to cancer cells than to normal cells. Radiation treatments work similarly and also can act essentially as “surgery by another means.” In either case, there is lasting damage to basic health. Normal, yet faster growing tissues, which include the tissues that make up the digestive tract, can be affected with implications for digestion. More than just taste and smell change under such circumstances. The fundamental nutritional needs of the body may not be met in important ways with implications for the nervous and immune systems. Today, gut-brain and gut-immune interactions are rapidly expanding areas of research as scientists try to unravel the links of the digestive system to other aspects of health.

There are yet other pieces to the puzzle. Researchers have had difficulty in pinpointing just why chemotherapy and radiation treatments are so lasting in their negative effects despite what seemingly should be adequate rest and nutrition. A paper published in 2014 may have solved at least some of this riddle. Interestingly, the answer goes back to a part of the body always considered to be a fundamental source of basic life energy and the ability of the body to renew itself: the marrow of the bones.

A key element is hematopoietic stem cells, which are cells created and stored initially in the bone marrow and which give rise to not only new red blood cells, but also to many types of immune cells. In fact, in their normal state hematopoietic stem cells from the blood and marrow appear to be ordinary white blood cells. Nevertheless, when called upon, these self-renewing cells also renew countless blood and immune cells. The U.S. National Institutes of Health on the Internet provide extensive and useful information regarding stem cells and interested readers should make use of such tools for further knowledge.

Ionizing radiation, such as that used in oncology treatments, can cause extensive fatalities among hematopoietic stem cells. In some cancer treatments, the damage to the hematopoietic stem cell population can be so extensive that cells and marrow must be transplanted from healthy donors. Unfortunately, to paraphrase an observation from industry, generally “original equipment” works best. This observation goes beyond radiation treatment because it is not just radiation that damages these cells. Chemotherapy and aging also damage hematopoietic stem cells.

Back to that 2014 paper: One challenge to the renewal of hematopoietic stem cells that is particularly linked to exposure to chemotherapy and radiation appears to be a reduction in the level of a particular protein that is necessary for hematopoietic stem cell renewal and activation. University of San Diego researchers, using an animal model, discovered that mice deficient in the protein beta-catenin lacked the ability to activate a pathway known as Wnt signaling. This failure led to impaired hematopoietic stem cell regeneration and poor bone marrow recovery after radiation. The result was a much-reduced rate of overall recovery inasmuch as there was reduced production of red blood cells and immune cells.

Damaged hematopoietic stem cells thus are a major aspect of reduced immune function and join other factors that have been identified in depressed immune function, such as damaged and non-responsive immune memory cells, cells whose very presence depresses the body’s ability to renew itself and to respond to immune challenges. This issue was discussed briefly in the February 2015 issue of Total Health under the heading, “Caloric Restriction, Fasting and Nicotinamide Riboside. ” Since the publication of that essay, new modified fasts have become available for those who cannot tolerate going three to four days with only water for sustenance. The research team that did much of the pioneering work on this topic has published instructions on how to perform a series of five-day fasts that can achieve most of the results of the original program with less strain and inconvenience.

Tai Li Wang: An Ancient TCM Herbal Solution
Fasting helps renew the immune system and hematopoietic stem cells by causing damaged and badly programed cells to be removed from the system. This approach resembles the employment of fasting in the Ayurvedic tradition to “activate the fundamental digestive fire (agni) of the body” to cleanse impurities/toxins that otherwise cannot be destroyed. However, fasting is not itself a solution to many aspects of poor digestive health, reduced adrenal function and the need for nutrition that supports the production of new blood and immune cells. These basic challenges characterize the typical impact of chemotherapy and radiation on health and contribute to the chronic nature of the fatigue and reduced immune function that are aftermaths of these treatments. For these purposes, Traditional Chinese Medicine (TCM) offers a number of sophisticated tonification therapies. One of the very best is the fermented herb mixture known as Tai Li Wang.

Tai Li Wang is a traditional Chinese herbal formula that some argue was created during the Warring States Period (475– 221 B.C.). As is true of many such “secret” formulas throughout Chinese history, it is difficult to trace back the actual history of the formula, which was first made “public” only in 1857 and has been officially approved by the Chinese Department of Health since 1992. Today, Tai Li Wang is registered in Hong Kong as a Tradition Chinese Herbal Medicine and is available in a number of hospitals in South China. Sea buckthorn and wolfberry are two of the primary ingredients, which provides a hint at the age and origin of the formula. It was during the Warring States Period that the Great Wall was begun and that Chinese civilization entered into extensive interchange with Central Asia. Sea buckthorn and wolfberry both are native to what today is the mountainous area of Tibet and Sinkiang in far Western China, but for much of the last 3,000 years was part of various Central Asian states. Moreover, this is a fermented formula and fermentation was practiced mostly in Western and Northern China due to the harsh winters. Hence, the formula most likely originated in Central Asia and entered China during this early period of contact.

Also referred to as a mulberry and sea-buckthorn beverage concentrate to reflect its two most prominent ingredients, Tai Li Wang is suggested for individuals under stress, including mental and physical stress, those recovering from surgery or illness, requiring a large nutritional boost, individuals suffering gastrointestinal problems, and those looking for an anti-aging tonic. Other ingredients include black sesame, black plum, goji, Buddha’s hand, Chinese white olive, fu ling, chrysanthemum and jujube.

Fermentation is an important aspect of the preparation of the herbs. Not only does fermentation protect and concentrate actives from the herbs, but it also leads to the formation of new beneficial compounds not initially present. The flavor of the drink is acidic or vinegar-like.

Employing classic TCM terminology, it is said that the Tai Li Wang formula Tonifies and rights the qi, enriches and nourishes the liver and kidneys, nourishes the blood and boosts the essence, moistens the lungs and relieves coughing, fortifies the spleen and harmonizes the stomach, disperses food and transforms stagnation, astringes the intestines and relieves diarrhea, quiets the heart and calms the nerves, engenders the liquids and quenches thirst, soothes the throat and relieves coughing.

Westerners usually are not familiar with TCM terminology and phrasing, yet the meaning of the above is not as obscure as at first it might seem. Briefly, the herbal tradition maintains that Tai Li Wang improves energy, supports the liver and kidney functions, increases blood components and supports their roles, is detoxifying, improves digestion and digestive functions (including being useful in both constipation and diarrhea), and is calming, including aiding sleep. In short, the formula is strengthening and balancing to the metabolism. Those who have tried Tai Li Wang (the flavor is challenging) can attest that some of its effects are realized within two or three days. For instance, the detoxifying and normalizing benefits for the gastrointestinal tract appear quickly. The stool becomes darkened, even tarry, indicating bile release (the body disposes of most toxins via the bile), yet at the same time there is a normalizing effect on stool consistency. Hence, there is a physical indication of a rapid impact on gut function, water balance and almost certainly a profound impact on the gut microbiome.

With regard to recovery after chemotherapy and radiation, supporting digestion, bowel function and detoxification provides a necessary and significant foundation. These medical treatments create various toxins as a result of free radical production and overt tissue damage while at the same time inhibiting the normal clearance mechanisms. Likewise, one reason for the weight loss that is characteristic of chemotherapy and radiation, apart from the loss of appetite, taste and smell, is that the body goes into overdrive in its attempts to repair the damage to normal tissues and quite literally cannot keep pace with the rate of destruction or the demands for removing damaged materials from the system.

Next in importance after the support of the gastrointestinal foundation of detoxification and health is Tai Li Wang’s impact on blood components. As noted above, chemotherapy and radiation destroy large numbers of hematopoietic stem cells, thus leaving the body lacking in precisely those cells necessary to renew both red blood cells and many types of immune cells. Supporting a return to health in these areas is exactly the benefit described by TCM with the phrase, “nourishes the blood and boosts the essence.” Not just many medical treatments, but, similarly, chronic excessive physical exertion and aging reduce the ability to renew the blood and immune cells. Experience from animal experiments and human clinical practice demonstrates that the TCM characterization is correct, that there is an increase in red blood cells and immune function without any danger of a rise in inflammatory responses. For instance:

… LACA mice of different ages given 12.5 g/kg of a mulberry decoction … by gavage daily for ten days in succession experienced marked increases in T-lymphocytes. The mulberry decoction acted as a moderate trigger for lymphocyte transformation. Rosette test results on mice showed that black plum increased immunity in domestic rabbits. Immunity testing (SOI) of super optimal doses of sheep red blood cells (SRBC) showed that suitable doses of goji polysaccharides significantly regulated suppressor T cells (Ts) in geriatric mice while increasing Ts activity. Pachyman strengthened immunity in regular and tumor-bearing mice and strengthened the macrophage phagocytic function in mice, resulting in significantly higher counts of antibody secretory cells in the spleen and increased ANAE positive lymphocyte counts in tumor-bearing mice. This served to antagonize the thymic atrophy….

In short, Tai Li Wang is an interesting fermented nutritional beverage that supports many physiological functions according to Traditional Chinese Medical categories, modern experiments and clinical usage in South China.

Conclusion
Despite tremendous medical advances, allopathic medicine has not done a good job in addressing the needs of recovery after chemotherapy, surgery and radiation. Chemotherapy and radiation cause lasting damage to the body, including to the ability of the gastrointestinal system and supporting organs to eliminate toxins and derive nutrients from food. Likewise, these treatments are detrimental to hematopoietic stem cells, the cells that are necessary for the renewal of red blood cells and many types of immune cells. The fermented Chinese herbal beverage known as Tai Li Wang, according to both animal work and clinical practice, offers an approach to nutritionally supporting healing and recovery that brings an ancient discovery to the modern world.

References:

1. Lento W, Ito T, Zhao C, Harris JR, Huang W, Jiang C, Owzar K, Piryani S, Racioppi L, Chao N, Reya T. Loss of â-catenin triggers oxidative stress and impairs hematopoietic regeneration. Genes Dev. 2014 May 1;28(9):995–1004.
2. “‘Fasting-mimicking diet’ may promote health and longevity,” June 21, 2015 found at http://www.medicalnewstoday.com/articles/295647.php
3. “Researchers Discover Fasting Can Significantly Prolong Life,” June 25, 2015 at http://readynutrition.com/resources/researchers-discover-fasting-can-significantly-prolong-life_25062015/
4. Hong Kong] Application For Registration Of Proprietary Traditional Chinese Medicine, Pharmacological Effects Report: Pharmacological Effects Report for “Tai Li Wang” Mulberry and Sea-buckthorn Beverage Concentrate.
5. http://www.angliatech.com/showcase/tailiwang/product_feature.php?lang=1

The post Herbal Support for Recovery from Chemotherapy and Radiation appeared first on Total Health Magazine.

Challenges to Bioavailability and Activity
Humans cannot directly transform glucosinolates into their more active forms. To a small and rather variable extent, intestinal microbes can perform this job, to be sure, yet the resulting bioactive compounds are formed below the areas in the gut with the most active uptake. This leaves plant sources of myrosinase as the limiting factor for cruciferous benefits. This is a major limitation for many reasons, including the effects of cooking, the nature of the ingested food form (the food matrix), other items ingested at the same time or shortly thereafter, and so forth and so on. For instance, cooking cruciferous vegetables inactivates myrosinase and decreases the release of isothiocyanates. Individuals who want to enhance their diets with broccoli supplements face yet more issues because these supplements most often do not contain any active myrosinase and therefore cannot produce the amount of the isothiocyanate sulforaphane that otherwise would be expected from sulforaphane glucosinolate.

Fortunately, a recent invention may have solved this problem. US Patent 9,017,666 provides a means of combining glucosinolates with myrosinase in a stable fashion for release in the small intestine. This patent, which is assigned to Jarrow Formulas of Los Angeles, provides for the creation of a dietary supplement that contains a standardized concentration of sulforaphane glucosinolate and the enzyme myrosinase water-extracted from broccoli seeds. Sulforaphane glucosinolate is metabolized to the isothiocyanate sulforaphane described above. Myrosinase facilitates this transformation when the two compounds are released together into a liquid environment. In terms of health this is important because sulforaphane has been demonstrated to be a potent inducer of Phase 2 detoxifying enzymes and to be a protector of DNA. The Phase 2 enzymes activated by sulforaphane may remain active as antioxidants in the tissues for up to three days.

A Multitude of Benefits
Looking specifically at broccoli, the primary precursor to sulforaphane commonly is known as sulforaphane glucosinolate (glucoraphanin). For at least a couple of decades, researches have been examining sulforaphane and other constituents of cruciferous vegetables as long-lasting antioxidants and much more.^1–3 These compounds work together to activate the body’s Phase 1 and 2 detoxification enzymes. Phase 1 enzymes make many toxins more water-soluble in preparation for their elimination from the body, but in the process can increase the toxicity of these compounds. To counter this outcome, Phase 2 enzymes bind and remove these now soluble toxins. Thus, the Phase 1 and 2 enzyme systems must be in balance to protect health.^4–6 Current research shows that sulforaphane glucosinolate initially activates Phase I enzymes. When metabolized to its isothiocyanate form as sulforaphane, the compound boosts the activities of Phase 2 enzymes and also is able to boost the level of thioredoxin, an enzyme that protects retinal cells of the eye against various types of oxidative attack.^7,8 In addition, sulforaphane

• supports blood pressure and cardiovascular health9
• is active in the area of gastric health, including inhibiting Helicobacter pylori 10–12
• promotes normal healthful inflammatory responses, including the suppression of COX-2, the activation of antioxidant enzymes and modulation of cytokine production^13–15
• enhances the regulation of cellular integrity^16–19
• inhibits advanced glycation end product-induced damage by reducing expression of a receptor for advanced glycation end products²⁰

Myrosinase-Activation of Sulforaphane Potential
Broccoli naturally contains myrosinase, broccoli’s own activator of sulforaphane production. However, during normal habits of consumption of broccoli and related vegetables because of cooking and other processing, generally it is left to bacterial action in the GI-tract to complete the metabolism of sulforaphane glucosinolate to sulforaphane. This is unfortunate because approximately 70 percent of sulforaphane preferentially is absorbed in the first two feet of the small intestine whereas most bacterial activation takes place below the area in the GI-tract best suited for sulforaphane absorption.²¹ Broccoli seed extracts, although often rich in sulforaphane glucosinolate, until now have not supplied the myrosinase needed to free sulforaphane.

Activation is only one half of the requirement for effective delivery of sulforaphane. If the two starting compounds are exposed to moisture prior to reaching the small intestine, sulforaphane glucosinolate and myrosinase will activate prematurely resulting in the loss of sulforaphane. Similarly, if sulforaphane glucosinolate and myrosinase are combined together in the acid environment of the stomach, the type of sulforaphane (sulforaphane nitrile) that is formed is largely inactive.²² This means that sulforaphane glucosinolate and myrosinase should be released only when they have reached the upper small intestine, which is the area in which sulforaphane primarily is absorbed.

The recent US Patent mentioned above solves the riddle of sulforaphane activation. It teaches how to combine sulforaphane glucosinolate and myrosinase in a stable manner and deliver them via acid resistant delayed release capsules known as DRcaps™. This facilitates the formation of sulforaphane in the upper part of the small intestine, the ideal environment for the formation and absorption of sulforaphane. BroccoMax®, the product produced by Jarrow Formulas, yields 8 mg pure sulforaphane potential per capsule. (in vitro tests)

Conclusion
Cruciferous vegetables have been shown to be sources of remarkable health-promoting substances and it long has been a goal of dietary supplements to replicate these benefits. Broccoli, as a source of sulforaphane glucosinolate that can be hydrolyzed to yield sulforaphane, is one of the most potent health promoters in the cruciferous family. However, without another key compound, myrosinase, the production of sulforaphane is small, inconsistent and dependent upon the action of intestinal bacteria. A recent US Patent has solved this issue and demonstrates a means to deliver the potential of sulforaphane glucosinolate as sulforaphane. Now a standardized amount of sulforaphane glucosinolate (glucoraphanin) can be delivered to the upper small intestine along with myrosinase, the enzyme in broccoli that metabolizes sulforaphane glucosinolate to sulforaphane. This means that the sulforaphane potential of broccoli seed extracts can be realized in the intestine at a point at which sulforaphane also is subject to its maximum uptake. At last, broccoli extracts can live up to the promise of delivering the most physiologically active compound that is derived from ingestion of broccoli, but from a supplement.

References

1. Shapiro TA, et al. Chemoprotective glucosinolates and isothiocyanates of broccoli sprouts: metabolism and excretion in humans. Cancer Epidemiol Biomarkers Prev. 2001 May;10(5):501–8.
2. Zhang Y. Molecular mechanism of rapid cellular accumulation of anticarcinogenic isothiocyanates. Carcinogenesis. 2001 Mar;22(3):425–31.
3. Shapiro TA, Fahey JW, Wade KL, Stephenson KK, Talalay P. Human metabolism and excretion of cancer chemoprotective glucosinolates and isothiocyanates of cruciferous vegetables. Cancer Epidemiol Biomarkers Prev. 1998 Dec;7(12):1091–100.
4. Myzak MC, Tong P, Dashwood WM, Dashwood RH, Ho E. Sulforaphane retards the growth of human PC-3 xenografts and inhibits HDAC activity in human subjects. Exp Biol Med (Maywood). 2007 Feb;232(2):227–34.
5. Myzak MC, Dashwood WM, Orner GA, Ho E, Dashwood RH. Sulforaphane inhibits histone deacetylase in vivo and suppresses tumorigenesis in Apc-minus mice. FASEB J. 2006 Mar;20(3):506–8.
6. Dashwood RH, Ho E. Dietary histone deacetylase inhibitors: from cells to mice to man. Semin Cancer Biol. 2007 Oct;17(5):363–9.
7. Gao X, Talalay P. Induction of phase 2 genes by sulforaphane protects retinal pigment epithelial cells against photooxidative damage. Proc Natl Acad Sci U S A. 2004 Jul 13;101(28):10446–51.
8. Tanito M, Masutani H, Kim YC, Nishikawa M, Ohira A, Yodoi J. Sulforaphane induces thioredoxin through the antioxidantresponsive element and attenuates retinal light damage in mice. Invest Ophthalmol Vis Sci. 2005 Mar;46(3):979–87.
9. Wu L, Noyan Ashraf MH, Facci M, Wang R, Paterson PG, Ferrie A, Juurlink BH. Dietary approach to attenuate oxidative stress, hypertension, and inflammation in the cardiovascular system. Proc Natl Acad Sci U S A. 2004 May 4;101(18):7094–9.
10. Galan MV, Kishan AA, Silverman AL. Oral broccoli sprouts for the treatment of Helicobacter pylori infection: a preliminary report. Dig Dis Sci. 2004 Aug;49(7-8):1088–90.
11. Haristoy X, Angioi-Duprez K, Duprez A, Lozniewski A. Efficacy of sulforaphane in eradicating Helicobacter pylori in human gastric xenografts implanted in nude mice. Antimicrob Agents Chemother. 2003 Dec;47(12):3982–4.
12. Fahey JW, Haristoy X, Dolan PM, Kensler TW, Scholtus I, Stephenson KK, Talalay P, Lozniewski A. Sulforaphane inhibits extracellular, intracellular, and antibiotic-resistant strains of Helicobacter pylori and prevents benzo[a]pyrene-induced stomach tumors. Proc Natl Acad Sci U S A. 2002 May 28;99(11):7610–5.
13. Woo KJ, Kwon TK. Sulforaphane suppresses lipopolysaccharide-induced cyclooxygenase-2 (COX-2) expression through the modulation of multiple targets in COX-2 gene promoter. Int Immunopharmacol. 2007 Dec 15;7(13):1776–83.
14. Zhang Y, Callaway EC. High cellular accumulation of sulphoraphane, a dietary anticarcinogen, is followed by rapid transporter-mediated export as a glutathione conjugate. Biochem J. 2002 May 15;364(Pt 1):301–7.
15. Ritz SA, Wan J, Diaz-Sanchez D. Sulforaphane-stimulated phase II enzyme induction inhibits cytokine production by airway epithelial cells stimulated with diesel extract. Am J Physiol Lung Cell Mol Physiol. 2007 Jan;292(1):L33–9.
16. Campbell L, Howie F, Arthur JR, Nicol F, Beckett G. Selenium and sulforaphane modify the expression of selenoenzymes in the human endothelial cell line EAhy926 and protect cells from oxidative damage. Nutrition. 2007 Feb;23(2):138–44. Epub 2006 Dec 5. Erratum in: Nutrition. 2007 Apr;23(4):378.
17. Pham NA, Jacobberger JW, Schimmer AD, Cao P, Gronda M, Hedley DW. The dietary isothiocyanate sulforaphane targets pathways of apoptosis, cell cycle arrest, and oxidative stress in human pancreatic cancer cells and inhibits tumor growth in severe combined immunodeficient mice. Mol Cancer Ther. 2004 Oct;3(10):1239–48.
18. Cho SD, Li G, Hu H, Jiang C, Kang KS, Lee YS, Kim SH, Lu J. Involvement of c-Jun N-terminal kinase in G2/M arrest and caspase-mediated apoptosis induced by sulforaphane in DU145 prostate cancer cells. Nutr Cancer. 2005;52(2):213–24.
19. Pledgie-Tracy A, Sobolewski MD, Davidson NE. Sulforaphane induces cell type-specific apoptosis in human breast cancer cell lines. Mol Cancer Ther. 2007 Mar;6(3):1013–21.
20. Maeda S, Matsui T, Ojima A, Takeuchi M, Yamagishi S. Sulforaphane inhibits advanced glycation end product-induced pericyte damage by reducing expression of receptor for advanced glycation end products. Nutr Res. 2014 Sep;34(9):807–13.
21. Sulforaphane Glucosinolate Monograph, Alt Med Review 2010.
22. Matusheski NV, Jeffery EH. Comparison of the bioactivity of two glucoraphanin hydrolysis products found in broccoli, sulforaphane and sulforaphane nitrile. J Agric Food Chem. 2001 Dec;49(12):5743–9.

The post Realizing the Health Benefits of Broccoli Supplements appeared first on Total Health Magazine.

Beware Controversial Findings with Flashy Headlines
Lately, there has been no shortage of headlines asserting that dietary supplements lack utility in helping to maintain health. Indeed, in a recent issue of Total Health ( Thursday, 01 May 2014) I debunked a claim that supplementing with omega-3 oils, primarily from fish oils, can increase prostate cancer. I argued that the conclusion is not supported by the evidence, most of which indicates that the opposite is true. In another article in a separate journal (Clouatre and Bell, J Nutr Food Sci 2013, 3:3), a coauthor and I rubbished claims that L-carnitine increases cardiovascular disease (the opposite is true). In these and similar instances, the supposed debunking of nutritional supplements had been presented as being based on scientific research. However, when examined closely, the research was found to be faulty, the conclusions did not follow from the research, the statistical model(s) used was/were misleading, the wrong questions were asked, or some combination of such issues came into play. The headlines might be attention-grabbing, but the research itself often was questionable on a number of grounds. Sadly, it is only the headlines that people tend to remember.

Earlier this year, yet another flashy headline appeared in a major journal asserting that multivitamin/mineral supplements are not useful for maintaining health. The responses from many of the most prestigious researchers in the field were not kind. One such response came from Balz Frei PhD, chairman of the Linus Pauling Institute at Oregon State University, Bruce Ames, PhD, of the Children’s Hospital Oakland Research Institute, Jeffrey Blumberg PhD, of Tufts University and Walter Willett MD, of the Harvard School of Public Health. These particular authors objected to the manner in which trials were selected for inclusion to prove that multivitamin-mineral supplements to not prevent chronic diseases and may actually cause harm. As noted by Balz Frei in an interview, these conclusions were arrived at by ignoring many beneficial effects that appeared in specific studies.

Frei pointed out that, among other benefits, multivitamins can help make sure that individuals meet the RDI of essential vitamins and minerals, e.g., “92 % of Americans do not consume the recommended amount of either vitamin D or E; 61 % don’t consume enough magnesium and 50% don’t take in enough calcium or vitamin A.” In addition, one large National Institutes of Health trial (Physician’s Health Study II) found that use of a multivitamin was associated with an 8 percent reduction in cancer incidence and reductions in total and nuclear cataracts by 9 and 13 percent, respectively. A casual observer might note that these results were found with physicians, a population of individuals that one might expect already to be taking better care of themselves than most of us, hence less likely to show benefits merely from supplementing with a multivitamin.

As Balz Frei argues in addition to the foregoing, multivitamin and mineral supplements not only offer inexpensive nutritional insurance, but also are remarkably safe. Dangerous dosage amounts are above clearly established tolerable upper levels of intake. Hence, merely following label instructions is a good guide to safe usage.

Is an Eight Percent Reduction in Cancer Meaningful?
One often-expressed line of criticism of dietary supplements made mostly by champions of drugs is that the benefits are not at a meaningful level. In many ways, this is a highly distorted line of criticism. Pharmaceuticals, of course, are expected to have very large effects in sick populations. Dietary supplements, in contrast, typically are tested in relatively healthy subject populations. Not surprisingly, the magnitude of the benefits found in the latter are likely to be much smaller than those that are found with drugs. After all, individuals who are reasonably healthy are just that, reasonably healthy. Moreover, drugs always come with numerous risks, whereas dietary supplements generally are extremely safe for most individuals.

A quick example indicates the differing scales of the two approaches: Weight loss in a morbidly obese patient (think of a person standing 5 feet 8 inches, yet weighing 300 pounds) happens very differently than in the average individual who only needs to lose few pounds, for example, 10 pounds. The morbidly obese patient on an effective compound can lose many pounds per week, whereas more normal-weight individuals not on a starvation diet simply will not lose more than 1 to 2 pounds (at the outside) per week for any extended period of time. Indeed, losing weight more rapidly than this can lead to problems, such as gallstones.

More about Vitamins, Herbs and Safety

In the November 2014 issue of Whole Foods Magazine
The supposed reason for the trial described in the medical journal was to “characterize hepatotoxicity and its outcomes from HDS [herbals and dietary supplements] versus medications.” This no doubt is a laudable goal for a study, but if this was the only goal, why did the study exclude the single largest source of liver complaints in the U.S., acetaminophen-induced liver injuries? Moreover, as Cory Hilmas points out, the “Hepatology” article was not even designed properly to prove that supplements were causing an increase in serious liver disease. For instance, it was not designed to weed out major confounders, such as alcohol use, prescription drug use, family history, etc.

It should be understood that the likelihood of liver injury from pharmaceuticals and supplements can be difficult, if not almost impossible to discover in advance even with massive clinical trials. Having reviewed adverse event reports myself in the case of kava kava, I can attest that the vast majority of such reports are incomplete and even in the drug trials liver injuries often do not show up until the drug has been on the market for months or years.

Does the Food and Drug Administration have a good program in place to uncover liver damage from dietary supplements? Yes, it does. Hilmas writes that FDA’s Center for Food Safety and Applied Nutrition (CFSAN) has the CFSAN Adverse Event Reporting System (CAERS) to determine whether liver issues are actually related to dietary supplements.

Conclusions
To return to our starting point, it is important to have scientific validation of the benefits of herbals and dietary supplements whenever such studies are available. For historic reasons, such studies are not available on a number of traditional herbal products and formulas. Nevertheless, good science is always to be welcomed, “good science” being the operative phrase. Science is an ongoing enterprise and it is subject to the limitations of all human projects. It easily can be skewed by the inappropriate inclusion and/or exclusion of data and trials, by the drawing of conclusions not properly backed by either the study design or the evidence collected, by unrecognized weaknesses in the evidence, and so forth and so on. All these factors need to be kept in mind the next time one is drawn in by an attention-grabbing headline, whether the headline purports to provide news either good or bad regarding herbals and dietary supplements.

References

1. Guallar E, Stranges S, Mulrow C, Appel LJ, Miller ER 3rd. Enough is enough: Stop wasting money on vitamin and mineral supplements. Ann Intern Med. 2013 Dec 17;159(12):850–1.
2. Frei B, Ames BN, Blumberg JB, Willett WC. Enough is enough. Ann Intern Med. 2014 Jun 3;160(11):807
3. http://www.nutraingredients-usa.com/Research/Nutrition-researchersshoot-holes-in-assertion-that-multivitamins-are-unnecessary Updated June 13, 2014.
4. http://www.nutraingredients-usa.com/Research/Holding-up-RCTsas-gold-standard-of-research-is-a-false-hope-and-conceals-statisticalpitfalls-experts-say
5. Navarro VJ1, Barnhart H, Bonkovsky HL, Davern T, Fontana RJ, Grant L, Reddy KR, Seeff LB, Serrano J, Sherker AH, Stolz A, Talwalkar J, Vega M, Vuppalanchi R. Liver injury from herbals and dietary supplements in the U.S. Drug-Induced Liver Injury Network. Hepatology. 2014 Oct;60(4):1399–408.
6. Clouatre DL. Kava kava: examining new reports of toxicity. Toxicol Lett. 2004 Apr 15;150(1):85–96.

The post Evaluating Dietary Supplement Research appeared first on Total Health Magazine.

BPH is hardly the lone prostate and sex hormone related issue that can be troubling to men. Aside from prostate cancer, which for most men is so slow growing as to not be life threatening, many men are concerned about low testosterone, which has its own repercussions. Two of the repercussions of low testosterone are a low level of muscle-maintaining free testosterone and elevated levels of estrogen produced from testosterone by a pathway referred to as the aromatase pathway. Fortunately, there are a number of safe natural compounds that can help to regulate both sides of this equation.

Protective herbs and nutrients have counterparts that increase the risks of various conditions. Some of these potentially damaging compounds are prescriptions given for unrelated conditions and this provides a rationale for being cautious about prescription drugs. What you do not know definitely can hurt!

PROTECTIVE AND SUPPORTIVE NUTRIENTS AND HERBS

Omega-3s
In 2013, experts slammed a claimed fish oil/omega-3 fatty acid intake link to prostate cancer as “scaremongering.” The trial in question purported to find increased risks for total prostate cancer as well as increased risks of both low-grade and high-grade prostate cancer, an increase of 71 percent in this latter category.² The responses were quick and brutal. One nutritionist (Duffy MacKay, vice president of scientific and regulatory affairs at the for Responsible Nutrition (CRN)) pointed out, quite correctly, that the findings of this study were based on blood level differences so small that “[t]his change [of 0.2%] literally could have occurred if somebody ate a fish sandwich on their way to get their blood drawn.”³ Both the consumers of the low and the high levels of long chain omega-3 fatty acids were within the normal blood range.

Others pointed out that the findings of the study clearly imply that men in countries with high levels of consumption of seafood, such as Scandinavia and Japan, should exhibit high levels of prostate cancer, yet the opposite is the case. Alan Ruth, PhD, CEO of the Irish Health Trade Association observed, “[i]n a 2010 meta-analysis of 31 studies published in the American Journal of Clinical Nutrition, the risks of prostate cancer diagnosis calculated for high fish consumption ranged from a 61% decrease in risk to a 77% increase in risk, and several showed no significant differences in risk at all…In the same meta-analysis, pooled data from four studies on fish consumption and death from prostate cancer (rather than diagnosis of prostate cancer) found a 63% decrease in risk for high fish consumption.”⁴

Especially interesting in this dust-up is the recent attempt to rehabilitate omega-6 fatty acids. In pre-modern times, the intake of omega-3 to omega-6 fatty acids in the diet typically was in the range of one-to-two, whereas today in the United States it regularly may be as low as one-to-twenty-five, with prostate cancer rates climbing steadily over the last 60 years. In this instance, a headline is revealing: “Corn oil, omega-6 could speed up prostate cancer.”⁵ Journal article titles are more prosaic, yet just as damning: “A high ratio of dietary n-6/n-3 polyunsaturated fatty acids is associated with increased risk of prostate cancer.”⁶

Barry Sears, who has written for years on the health effects of fatty acids, both good and bad, tartly comments in his blog, “Omega-3 fatty acids and prostate cancer? Oh, really?”⁷ Among other things, Sears demonstrates how easily a statistically significant blood reading of fatty acid profiles can be attached to otherwise clinically irrelevant findings. The take away message in this case is that the experience around the world repeatedly has been that prostate risks, especially death from prostate cancer, are lower in matched populations that consume more fish. There is nothing in recently published research that should make us doubt that improving the omega-3 to omega-6 ratio in our diets is a good goal at which to aim.

Grape Skin Extract & Resveratrol
In many areas in the US and the United Kingdom (Scotland has not yet opted out of the Union), one cannot visit a doctor without being queried about alcohol intake and then the required lecture on the evils of alcohol. The distinction as to the source of alcohol in the diet routinely drops out despite the fact that red wine has been recognized in Europe for centuries as exhibiting various health benefits and little downside as long as consumed in moderation. It turns out that red wine, often thought of in terms of the heart, may benefit the prostate, as well.

The trick to the studies is that the researchers must work vigorously to screen for the different sources of alcohol over the course of a man’s life. If this is done, then the research is likely to confirm that a glass of red wine per day may be protective against the risk of prostate cancer.⁸ Less clear is which compounds in red wine are protective. Perhaps many are. A recent study on grape skin extract and resveratrol identified several protective mechanisms of action.⁹ Some of the factors linked to resveratrol have been known for years, whereas other mechanisms and, similarly, the benefits of other red wine compounds, are being vigorously researched. Grape seed components (proanthocyanidins) are another example of a source of anti-cancer benefits.¹⁰ Given the huge volume of papers being published today on the health-protective benefits of red wine and its ingredients, it is a reasonable conclusion that most men may benefit from one or two glasses of red wine per day consumed with meals.

Quercetin & EGCG
The dietary bioflavonoid quercetin is well known to readers of this magazine, as is epigallocathechin gallate (EGCG). Both compounds are considered to be health protective and quercetin, in particular, is known to improve the uptake (bioavailability) and the benefits of many other compounds found in the diet and in herbs. Papers routinely show greater efficacy or even benefits where none initially were found, when quercetin is combined with resveratrol, with sulphorafane, with EGCG, etc. One of the more interesting recent findings is that these combinations sometimes not only can help to prevent the transformation of cells from precarcinogenic stages to active cancer, but also can interfere with or eliminate entirely cancer stem-cell characteristics. Cancer stem cells are the ultimate source of cancer self-renewal, so this action by the combination of quercetin and EGCG is a warm recommendation.¹¹

Bitter Melon
Bitter melon has received quite a bit of publicity recently with regard to pancreatic cancer. It would be unfortunate were the exploration to end there. Several researchers have reported that treatment of bitter-melon-related products in a number of cancer cell lines induces cell cycle arrest and apoptosis without affecting normal cell growth.¹² Researches targeted specifically at prostate cancer have demonstrated that the impact of bitter melon extends to this area.¹³ Admittedly, bitter melon is not a staple at the American table. Perhaps that should change. See my earlier article, “Going WILD with Bitter Melon for Blood Sugar Support.”¹⁴

Pomegranate
Pomegranate is a fruit long associated with healing and medicine. Indeed, the pomegranate is on the crest-of-arms of the British Royal Society of Medicine and of many other ancient organizations devoted to healing. A quick look at the PubMed database shows that the keywords “pomegranate” and “prostate” bring up 60 studies. Many of these studies have been promising, especially when pomegranate was added to other ingredients with related and differing mechanisms of action. For instance, in 2013 the polyphenol rich whole food supplement Pomi-T® (pomegranate seeds, green tea, broccoli, and turmeric) was reported to have a direct anti-cancer effect in men with prostate cancer.15 These results were confirmed in a larger clinical trial published in 2014.¹⁶

Thymoquinone and Black Seed
Few Americans have heard either of black seed or thymoquinone (TQ). The former is famous for healing in the areas in which it grows naturally, meaning much of the eastern Mediterranean through the Near and Middle East all the way to India. Mohammed is reputed to have said that the seed cures every condition except death itself.

With regard to the prostate, black seed is useful for both BPH and in preventing prostate cancer induction. One of the important ingredients in black seed oil, thymoquinone, promotes healthy apoptosis in prostate cells and therefore helps the body to regulate the size and health of the prostate.^17,18 Similar effects have been found in, for example, breast cancer, so TQ has a broad spectrum of applications.¹⁹

Cactus Flower
A couple of decades back, the herbal extract chrysin was introduced to the athletics and body building world as an answer to improving free testosterone levels and reducing the pathway (aromatase) that transforms testosterone to estrogen. Chrysin has some benefits, as long as one does not expect too much and is willing to focus on the anxiolytic qualities of the compound (found in passion flower). However, much more successful compounds for this purpose of increasing free testosterone, and so forth, have been found. One of these is an extract of cactus flower (Opuntia ficus-indica).

I ran across this almost a decade ago being sold in Germany and Israel for BPH,²⁰ but at the time could not find a reliable source of supply. Since then, a friend with whom I was working took this item and continued to dig until he found a reliable source that he could market as increasing serum free testosterone levels and reducing aromatase (reducing estrogen production and inhibiting the binding of dihydrotestosterone/DHT.) As my friend writes at his website, based on preliminary laboratory research, “Opuntia flower extract (1 mg/ml concentration) inhibited over 80% of the activity of 5-alpha reductase in human prostate tissue homogenate and inhibited over 80% of aromatase activity in human placenta tissue homogenate.”²¹ This particular product also contains supporting ingredients, such as an extract of stinging nettle root.

Some Prostate-Questionable Foods and Pharmaceuticals Now for a few items that men may want to remove from their daily habits or environment.

• Non-and low-fat milk (but not whole milk or other dairy products) intake by men is linked to higher rates of prostate cancer²²
• Long-term use of statins increases the risk of prostate cancer²³
• Oral contraceptive use is associated with prostate cancer—this refers to these contraceptives getting into the environment at large and not to use by one’s partner²⁴

Conclusion
There are protective foods, nutrients and herbs of which men should take advantage to maintain and regain prostate health as well as improve other parameters of health and performance. Omega-3 fatty acids and the active compounds found in red wine (grape skin anthocyanidins and other compounds, resveratrol, grape seed proanthocyanidins, quercetin), green tea (EGCG) and bitter melon are on this short list. More exotic are black seed and thymoquinone as well as cactus flower extract. For the most part, these can be characterized as special foods since they can be consumed over the long term and have few or no downsides even when consumed chronically in large amounts. Indeed, this should be the goal—a little prevention is always worth a whole lot of cure.

References

1. 1. 1. F. Hinman, Benign Prostatic Hypertrophy. New York: Springer-Verlag, 1983.
      2. Brasky TM, Darke AK, Song X, Tangen CM, Goodman PJ, Thompson IM, Meyskens FL Jr, Goodman GE, Minasian LM, Parnes HL, Klein EA, Kristal AR. Plasma phospholipid fatty acids and prostate cancer risk in the SELECT trial. J Natl Cancer Inst. 2013 Aug 7;105(15):1132– 41. doi: 10.1093/jnci/djt174.
      3. Experts slam omega-3 link to prostate cancer as overblown ‘scaremongering.’ http://www.nutraingredients.com/content/view/print/796071
      4. Ibid.
      5. http://www.foodnavigator-usa.com/news/printNewsBis.asp?id=65537
      6. Williams CD, Whitley BM, Hoyo C, Grant DJ, Iraggi JD, Newman KA, Gerber L, Taylor LA, McKeever MG, Freedland SJ. A high ratio of dietary n-6/n-3 polyunsaturated fatty acids is associated with increased risk of prostate cancer. Nutr Res. 2011 Jan;31(1):1–8. doi: 10.1016/j.nutres.2011.01.002.
      7. http://zonediet.com/blog/2013/07/
      8. A glass of red wine a day keeps prostate cancer away?
      9. Hudson TS, Hartle DK, Hursting SD, Nunez NP, Wang TT, Young HA, Arany P, Green JE. Inhibition of prostate cancer growth by muscadine grape skin extract and resveratrol through distinct mechanisms. Cancer Res. 2007 Sep 1;67(17):8396–405.
      10. Raina K, Singh RP, Agarwal R, Agarwal C. Oral grape seed extract inhibits prostate tumor growth and progression in TRAMP mice. Cancer Res. 2007 Jun 15;67(12):5976-82.
      11. Tang SN, Singh C, Nall D, Meeker D, Shankar S, Srivastava RK. The dietary bioflavonoid quercetin synergizes with epigallocathechin gallate (EGCG) to inhibit prostate cancer stem cell characteristics, invasion, migration and epithelial-mesenchymal transition. J Mol Signal. 2010 Aug 18;5:14. doi: 10.1186/1750–2187–5–14.
      12. Nerurkar P, Ray RB. Bitter melon: antagonist to cancer. Pharm Res. 2010 Jun;27(6):1049–53. doi: 10.1007/s11095–010–0057–2.
      13. Ru P, Steele R, Nerurkar PV, Phillips N, Ray RB. Bitter melon extract impairs prostate cancer cell-cycle progression and delays prostatic intraepithelial neoplasia in TRAMP model. Cancer Prev Res (Phila). 2011 Dec;4(12):2122–30. doi: 10.1158/1940–6207.
      14. TotalHealth Online: Going Wild With Bitter Melon for Blood Sugar Support
      15. Goodman A. High Marks for Nutritional Supplement in Patients with Localized Prostate Cancer. Value-Based Cancer Care. September 2013 Vol 4, No 7.
      16. Thomas R, Williams M, Sharma H, Chaudry A, Bellamy P. A doubleblind, placebo-controlled randomised trial evaluating the effect of a polyphenol-rich whole food supplement on PSA progression in men with prostate cancer-the UK NCRN Pomi-T study. Prostate Cancer Prostatic Dis. 2014 Mar 11. doi: 10.1038/pcan.2014.6.
      17. Kaseb AO, Chinnakannu K, Chen D, Sivanandam A, Tejwani S, Menon M, Dou QP, Reddy GP. Androgen receptor and E2F-1 targeted thymoquinone therapy for hormone-refractory prostate cancer.Cancer Res. 2007 Aug 15;67(16):7782–8.
      18. Kumar AP, Sethi G, Tan KH. Thymoquinone: potential cure for inflammatory disorders and cancer. Biochem Pharmacol. 2012 Feb 15;83(4):443–51. doi: 10.1016/j.bcp.2011.09.029.
      19. Rajput S, Kumar BN, Sarkar S, Das S, Azab B, Santhekadur PK, Das SK, Emdad L, Sarkar D, Fisher PB, Mandal M. Targeted apoptotic effects of thymoquinone and tamoxifen on XIAP mediated Akt regulation in breast cancer. PLoS One. 2013 Apr 17;8(4):e61342. doi: 10.1371/journal.pone.0061342.
      20. Palevitch D., Earon G., Levin I., Treatment of benign prostatic hypertrophy with Opuntia ficus-indica (L.) Miller. Journal of herbs, spices & medicinal plants. J. herbs spices med. plants 1993;2(1):45–49.
      21. http://cleanmachineonline.com/science/how-it-works/ drawing upon Jonas A, Rosenblat G, Krapf D, Bitterman W, Earon G, Neeman I. Efficacy of cactus flowers miller treatment in benign prostatic hyperplasia due to inhibition of 5a reductase activity, aromatase activity and lipid peroxidation. HerbaMed paper; undated.
      22. Park SY, Murphy SP, Wilkens LR, Stram DO, Henderson BE, Kolonel LN. Calcium, vitamin D, and dairy product intake and prostate cancer risk: the Multi-ethnic Cohort Study. Am J Epidemiol. 2007 Dec 1;166(11):1259–69.
      23. Chang CC, Ho SC, Chiu HF, Yang CY. Statins increase the risk of prostate cancer: a population-based case-control study. Prostate. 2011 Dec;71(16):1818–24. doi: 10.1002/pros.21401.
      24. Margel D, Fleshner NE. Oral contraceptive use is associated with prostate cancer: an ecological study. BMJ Open. 2011 Nov 14;1(2):e000311. doi:10.1136/bmjopen–2011–000311.

The post Supplements for Prostate Health and Testosterone Support appeared first on Total Health Magazine.

In point of fact, many common foods have as great or greater an impact upon numerous medical conditions as do the vitamins and herbs that have been singled out. Examples of this will be given shortly. In considering these examples, the reader should be aware they are not exhaustive. They are being offered as evidence for a number of points worth pondering. First, what is revealed by the current focus upon the medical interactions of popular supplements? Second, if quite a number of foods pose the threat of similar interactions, does a lack of focus on or concern with dietary factors suggest that the diet of the average American is highly restricted in terms of food choices? Third, is it the case that many conditions for which drugs are readily prescribed for chronic use in this culture might be better treated by simple changes in the diet and/or the use, as first choice, of vitamins, herbs and other supplements which have negligible side effects?

Vitamin D One More Time
TotalHealth magazine over the past few years has been vigilant in examining controversial attacks on vitamin supplements and it is disappointing to many of us that wrong-headed analyses continue to be picked up and presented uncritically by both professional journals and the popular press. USA Today (January 23, 2014) is a good example of this as it states unambiguously that studies and reviews of vitamin D have found no “significant benefits for heart health, cancer prevention or even bone health in healthy people.” The journal article that prompted these comments, large meta-analysis just published in the British medical journal Lancet is blunt in its assessment of vitamin D:¹ “Available evidence does not lend support to vitamin D supplementation and it is very unlikely that the results of a future single randomized clinical trial will materially alter the results from current meta-analyses.”

The response from a number of primary vitamin D researchers to this and other recent meta-analyses has been withering. This includes the remarks of Dr. Michael Hollick, the scientist responsible for identifying the major circulating form of vitamin D in serum —25-hydroxyvitamin D3—which is the form of vitamin D measured medically to assess vitamin D status. Dr. Hollick terms the recent papers flawed and “silly.” Dr. Hollick’s views are reported by Dr. Mercola on his website which provides an elaborate critique of the recent vitamin D papers. Another researcher who roundly dismisses the recent studies is Dr. Cedric Garland of the University of California at San Diego Moore’s Cancer Center. His comments cover both the Lancet paper already mentioned and another recent meta-analysis:

This meta-analysis is nothing new and is already obsolete since it is mainly based on old papers that used too little vitamin D to expect any effect. A New Zealand study saying we should only supplement people with vitamin D deficiency and evidence of bone loss is equally wrong. Virtually everyone in New Zealand, and most adults in the U.S., are vitamin D deficient by modern criteria, being below 32 ng/ml.

The reality is that we now know that they are deficient with regard to extra-skeletal effects of 25(OH)D if their serum level is below 40 ng/ml. These papers should be disregarded as obsolete work. We are moving into a new era of using vitamin D3 in doses no less that 4,000 IU/day for people aged 9 years and older… Studies using less than 4,000 IU/day are on the verge of obsolescence.

In other words, the studies culled and used as the basis of the recent meta-analyses of vitamin D were themselves inadequate because designed around totally inadequate vitamin D daily dosages. Moreover, one does not need to look far for at least one very major review that disagrees with the conclusions of the negative meta-analyses in the most fundamental way. A Cochrane review published just this year on vitamin D and mortality gives an answer that seems more than sufficient to warrant another look at vitamin D, at least in its D3 form:²

Vitamin D3 seemed to decrease mortality in elderly people living independently or in institutional care. Vitamin D2, alfacalcidol and calcitriol had no statistically significant beneficial effects on mortality.

Blood Thinning Drugs
Another point of current controversy involves both vitamins/ vitamin-like compounds and various herbs. Many aging individuals are treated with anti-coagulants or “blood thinners” to reduce the risks of stroke and blood clots. One popularly prescribed such drug is Coumadin (warfarin). Drug interactions with any of the anticoagulants are quite common, including with such everyday items as alcohol and aspirin. The usual side effects involve too free bleeding and show up as such things as easy bruising, frequent nosebleeds, dark urine and tarry stools. Needless to say, excessive bleeding can be life-threatening under certain conditions. Interactions with anticoagulants are so common that some pharmaceutical experts caution against taking any new drug, including over-the- counter items such as aspirin, without first speaking with a doctor or pharmacist.

Ginkgo biloba extracts, particular examples of which in a number of clinical trials currently are being reaffirmed for cognitive health (but only in the case of certain extracts)3, possibly present a problem for those taking anticoagulant drugs largely because these extracts perform many of the same tasks as those drugs and much more. Ginkgo extracts improve the blood flow through the artery which serves the heart, improve circulation in the brain and more generally throughout the body, increase the clearance of toxins from the system, and protect the body against what is known as platelet-activating factor (PAF). PAF was only discovered in 1972, and since that time scientists have come to realize that it is involved in disturbances ranging from internal blood clots (often leading to heart attacks and strokes) to allergic reactions and asthma.⁴

Problems with excessively “sticky” blood are much more common in the United States than they are in many other countries around the world, such as in Japan. Diet appears to be by far and away the most significant factor in this. A quite large number of foods “thin” the blood. Food sources of omega-3 fatty acids, which include many cold-water ocean fish as well as walnuts and a few other items, all tend to increase clotting time. All members of the onion and garlic families act as blood thinners, especially if eaten regularly and in quantity. The same is true of the mo-er (black tree fungus) and reishi mushrooms, both of which can be purchased in markets, which carry specialty mushroom and Asian vegetables. Another natural blood thinner is hawthorn. Hawthorne, which is found primarily as an extract in this country, is the basis for some popular beverages in Asia and often taken as a tea in Europe. Red wine, especially if it is high in the antioxidant resveratrol, may increase coagulation time. The quinine found in tonic water will increase or prolong the actions of Coumadin and may have its own blood thinning effects. Grapefruit is notorious for reducing the clearance of warfarin-like compounds and therefore increasing the risk of hemorrhage.^5,6

A great many herbs, spices and digestive aids can exercise significant anticoagulant effects. These include cayenne pepper, bromelain from eating pineapple fruit and stem, papain from papaya, and likely paprika and most chili peppers. Ginger root, which is eaten in quantity in Indian and Oriental cuisines, can strongly inhibit clotting. So can its relative, tumeric, which is used widely in curries and a source for purified curcumin. Vitamins and vitamin-like compounds, as mentioned above, can lead to similar problems. These compounds include vitamin E, tocotrienols, omega-3 fatty acids, lipoic acid and many more.

Both Chinese and Indian (Ayurvedic) medicine would greatly expand these lists of foods and herbs which can increase clotting time, but, even as things stand, it should be clear that diet likely is the predominant factor by far in determining the activity of several elements in the blood which control clotting time. Of course, there are at least as many dietary factors which can influence blood coagulation in opposition to Coumadin as those which are additive.

Changing the Rate of Drug Clearance
Many drugs (including some protease inhibitors, calcium channel blockers, and oral contraceptives) are metabolized by the cytochrome P450 3A4 (CYP3A4) metabolic pathway, which is active in the liver. Grapefruit has already been mentioned as influencing this pathway; it contains the compound naringenin, which is one of the most powerful of common compounds in affecting CYP3A4. The herbal supplements, which presently are the most strongly implicated are goldenseal (Hydrastis canadensis), St. John’s wort (Hypericum perforatum), and cat’s claw (Uncaria tomentosa).⁷ Black pepper extracts, similarly, influence cytochrome P450 and other elements involved in drug clearance.

The ability to zero-in on this enzyme system through special research techniques, unfortunately, in many ways is a bit misleading. How much difference does it make in practice whether the clearance of a drug is delayed as opposed to its absorption being greatly enhanced? Black pepper, cayenne pepper, ginger and long pepper all either strongly increase absorption of other compounds and/or influence cytochrome P450. Some sources of lecithin, such as eggs, may similarly increase the uptake of certain drugs. Alcohol typically enhances the effects of many drugs, whether by increasing absorption, producing its own additive effects, or delaying clearance.

Quite a remarkable number of items in the diet can interfere with many drugs. Some interfere directly with absorption, as do the tannins and fibers found in many fruits and vegetables. Others do so indirectly by activating overall metabolism, liver and/or kidney functions.

Why Look to Dietary Choices Last?
Herbs, of course, do have many powerful effects upon the body and should not be treated as if they are innocuous merely because they are “natural.” However, also missing in American culture at large is an awareness that it is relatively easy to intervene in many common conditions without resorting to prescription drugs. In point of fact, other than a quite narrow range public health messages regarding primarily fats and fiber in the diet, we do not tend to think of diet as having much of an impact upon health at all. There is no reservoir of knowledge in everyday American culture regarding the health uses of foods and herbs, unlike the cultures of Asia and even Europe. Moreover, the U.S. heavily subsidizes the growth and production of many foodstuffs used in “fast foods” (corn, wheat, sugar beets, etc.) while doing nothing to reduce the cost to consumers for fresh fruit and vegetables, i.e., items that are healthful rather than being merely sources of calories.

Indeed, there are entire classes of medications sold extremely widely in the United States for which there appears to be no need in many other cultures. One class which immediately comes to mind is that of the acid reflux / heartburn /antacid medications, whether over-the-counter or prescription. The entire notion that there are health problems stemming from the production of excess stomach acid is surely an odd one given the fact that we typically have no such problems when we are young and produce plenty of stomach acid, yet such problems in this culture are common in middle age and later, i.e., at the point at which the ability to produce stomach acid has already begun to decline markedly. What has really happened is that the muscle that closes off the top of the stomach and prevents its contents from flowing back up the esophagus has weakened. Items that reduce the production of stomach acid at the same time prevent the complete digestion of proteins in the stomach, but, again, do nothing to strengthen the muscle that controls acid reflux. Interestingly enough, acid reflux is virtually unknown in much of Asia where ginger is commonly used as a part of meals. Ginger just happens to strengthen the esophageal sphincter.

In truth, the American diet tends to be extremely narrow in the range of the foods eaten. “Fast foods” such as a burger and fries garnished with a little bit of cold slaw have become increasingly important sources of dinner and supper for the average American, and therefore it is hard to argue that our range of foods consumed daily is large. Some authorities estimate that one half of all meals are eaten outside the home, mostly at fast food restaurants. Aside from the obviously poor nutrition supplied by such choices, it is also the case that most of the otherwise readily available foods that might be used to influence many health conditions are either missing or very badly represented. We grow these foods, we just don’t eat them. Hence the observation by one Tibetan doctor to the effect that we seemed to have only two flavors in this culture, salty and sweet.⁸

This returns us to our starting point. Were the average American consuming a truly varied diet, the American medical profession likely would be more aware of the impact of foods upon health. Likewise, there is the curiously dichotomous thinking of many of those who are medically trained to the effect that herbs are either without any benefit, on the one hand, or likely to be a threat to prescribed pharmaceutical drugs, on the other hand. According to this way of thinking, items are either foods or drugs. Foods support the structure and functions of the body, whereas drugs intervene. As long as herbs could be seen as being without effect, they could be relegated largely to the foods category, i.e., at best innocuous and a waste of money in terms of health benefits. Once it is admitted that herbs might have benefits, they must be treated like drugs and viewed as possessing a host of powerful side effects and drug interactions.

The problem is that even everyday foods can have quite powerful effects upon the body. So why not make use of these food effects as a first line of treatment, herbs as a second line, and drugs only when all else fails?

References

1. Reid IR, Bolland MJ, Grey A. Effects of vitamin D supplements on bone mineral density: a systematic review and meta-analysis. Lancet. 2014 Jan 11;383(9912):146-55.
2. Bjelakovic G, Gluud LL, Nikolova D, Whitfield K, Wetterslev J, Simonetti RG, Bjelakovic M, Gluud C. Vitamin D supplementation for prevention of mortality in adults. Cochrane Database Syst Rev. 2014 Jan 10;1:CD007470.
3. Lewis JE, Melillo AB, Tiozzo E, Chen L, Leonard S, Howell M, Diaz J, Gonzalez K, Woolger JM, Konefal J, Paterson E, Barnes D. A double-blind, randomized clinical trial of dietary supplementation on cognitive and immune functioning in healthy older adults. BMC Complement Altern Med. 2014 Feb 4;14(1):43.
4. Murray, Michael T. “The Healing Power of Herbs,” 2nd edition (Prima Publishing, Rocklin, California: 1995.)
5. Brinker, Francis. “Herb Contraindications and Drug Interactions.” Revised 2nd edition. (Eclectic Medical Publications, 1998.)
6. Mindell, Earl and Hopkins, Virginia. “Prescription Alternatives.” (Keats Publishing, 1998.)
7. Budzinski JW, Foster BC, Vandenhoek S, Arnason JT. An in vitro evaluation of human cytochrome P450 3A4 inhibition by selected commercial herbal extracts and tinctures. Phytomedicine. 2000;7(4):273-82.
8. Yeshi Donden. “Health Through Balance.” Snow Lion Publications, 1986.)

The post Controversial Vitamins? Controversial Herbs? appeared first on Total Health Magazine.