Value of dietary changes for heart health – questioned

This month an astounding report was published in the Annals of Internal Medicine claiming little if any reduction in heart disease outcomes is obtained through Nutritional Supplements and Dietary Interventions. Unfortunately for me, I know too much to let this claim stand without a rebuttal.

The study published July 9, 2019

This study[1] was aimed at finding the true effects of nutritional supplements or dietary interventions on all causes of death or heart disease outcomes such as heart attack death, heart attack, stroke, and heart artery disease. These study authors looked only at randomized controlled trials (RCTs) and their meta-analyses—which indeed are the most powerful data to draw from, but misses a lot of data that should still be considered. While there are 14 investigators named in the study title, only two independent investigators abstracted data, assessed the quality of evidence, and rated the certainty of evidence. In all, 992,129 participants were included. The problem is that who knows what bias they had while selecting data and analyzing its quality?

The authors begin by stating, “The role of nutritional supplements and dietary interventions in preventing mortality (death) and cardiovascular disease outcomes is unclear.” Really? OK, then now they are going to build upon that false premise.

Their findings were that “Reduced salt intake (in people without high blood pressure), omega-3 long-chain polyunsaturated fatty acid (LC-PUFA) use, and folate supplementation could reduce risk for some cardiovascular outcomes in adults” and that “Combined calcium plus vitamin D might increase risk for stroke.” Then they accurately state, “Other nutritional supplements, such as vitamin B6, vitamin A, multivitamins, antioxidants, and iron and dietary interventions, such as reduced fat intake, had no significant effect on mortality or cardiovascular disease outcomes (very low- to moderate-certainty evidence).”

Can you detect here the confusion they created with this report? If not, let me explain.

Confusion created

This study has led to prominent online postings[2] with such titles as “Supplements and dietary interventions offer little (if any) protection against heart disease, study finds.”

They have confused many people to conclude that the supplements and the (limited) dietary interventions these authors evaluated were important data to evaluate. Notice that the investigators did not study nutrient rich whole (and mostly raw) foods, i.e. “plant-based” diets which are well known to cause a tremendous effect on lowering death rates, heart disease and stroke. The investigators did also not evaluate the supplements known to reduce cardiovascular disease risk. I will show you what I mean, and why this recent online article[3] is absolutely false and misleading, which stated, “Nutritional supplements and dietary interventions provide no protection against cardiovascular disease and early death, according to a major new analysis of dozens of studies on the topic, which was published

Monday in the Annals of Internal Medicine.” And see how the subsequent sentence in that report is also incorrect: “The only possible exceptions were a low-salt diet and two supplements — folate (folic acid) and omega-3 fatty acids (fish oil).” That’s ridiculous. Let’s look at the data.

Supplements and dietary interventions are proven to be effective

Let’s look at some evidence proving the cardioprotective effects of nutrient-rich, plant-predominate diets.

First, there is the work of the Lifestyle Heart Trial directed by Dr. Dean Ornish and associates. Their findings reported[4] in the Journal of the American Medical Association nearly 20 years ago concludes, “In summary, these ambulatory patients were able to make and maintain comprehensive changes in diet and lifestyle for 5 years and showed even more regression of coronary atherosclerosis after 5 years than after 1 year as measured by percent diameter stenosis. In contrast, patients following more conventional lifestyle recommendations showed even more progression of coronary atherosclerosis after 5 years than after 1 year, and had more than twice as many cardiac events as patients making comprehensive lifestyle changes.”[5]

Then there is the work of T. Collin Campbell and colleague in the Cornel China Study[6] who reported their findings approximately 20 years ago. More than 20 researchers spanning 40 years of compiled mortality data from both animal studies and approximately 650,000 rural Chinese was collected and analyzed from 130 villages in rural mainland China. This data was correlated with nutritional factors where fiber intake was 3 times higher and animal protein intake at approximately 10% of the U.S. intake. They found coronary artery disease mortality was 16.7-fold greater for U.S. men and 5.6-fold greater for U.S. women than for their Chinese counterparts. They stated that the coronary artery disease death rates for both genders in rural China were inversely associated with the frequency of intake of green vegetables and monounsaturated fatty acids. Correspondingly, they found blood biomarkers (apolipoproteins) were lowered as plant protein, legume, and light-colored vegetable intake increased. Plus, there was no evidence of a threshold beyond which further benefits did not accrue with increasing proportions of plant-based foods in the diet.

How about this interesting study reported in the British Medical Journal in 1996.[7] In this study, 4336 men and 6435 women were recruited through health food shops, vegetarian societies, and magazines. After a mean of 16.8 years follow up, overall the cohort of healthy eaters had a mortality about half that of the general population. Within the cohort, daily consumption of fresh fruit was associated with significantly reduced deaths from heart disease, stroke and all causes combined.

Supplements to lower heart disease risk

We know that synthetic vitamins don’t do much for us. The study authors name vitamin B6, vitamin A, multivitamins, iron and antioxidants [but which antioxidants they did not say] as supplements that don’t make a difference for heart disease and death reduction.

Let’s look at ones that are proven to work:

  • Nutrient IP-6: this is a food nutrient called inositol hexaphosphate (IP6, or “phytate”) that helps keep calcium out of the artery walls and in the bones where it should be. A 2006 animal study reported in Frontiers in Bioscience showed a highly significant reduction in the calcium content of aorta and heart tissue when treated with IP-6.[8] Human studies mirror this finding; 1,000 mg IP6 daily.[9] [10]

  • Vitamin K2: In addition to IP6, vitamin K2 (menaquinone) activates proteins that prevent excess calcium deposition in your blood vessels.[11] [12] There are the two forms of vitamin K2 called MK-7 and MK-4 “shuttle” calcium out of your blood stream and into your bones. Vitamin K2 at 100-150 mcg daily decreases C-reactive protein (non-specific marker of inflammation), increases arterial elasticity, decreases arterial plaque,[13] decreases coronary heart disease and total mortality. The 7-year prospective Rotterdam Study[14] of 4807 subjects (2004) as well as a later 2009 prospective study[15] of 16,057 women supplementing with Vitamin K2 showed significant reduction in heart attack (at 22-50 mcg daily) and all-cause deaths (at 30-40 mcg daily).

  • L-Arginine at 6 grams daily triggers the natural arterial secretion of nitric oxide which dramatically relaxes arterial smooth muscle for optimal blood flow and has arterial wall anti-inflammatory effects,[16] [17] [18] which is even more effective in salt-sensitive persons.[19]

  • L-Taurine has pronounced beneficial heart health effects including its blood pressure lowering effect,[20] [21] best taken at 3 grams twice daily.

  • R-(alpha) lipoic acid lowers blood pressure and improves arterial wall dysfunction through beneficial effects on nitric oxide (the vasodilator) and other mechanisms at the optimal dose of 100-200 mg daily.[22]

  • Alpha lipoic acid lowers blood pressure;[23] improves endothelial dysfunction; [24] reduces reactive oxygen species and oxidative stress[25] and has other cardio-protective mechanisms.[26] The optimal dose is 300-600 mg twice daily.

  • D-ribose[27] improves angina, heart failure, arrhythmias, weakness, and fatigue at 5 grams 3-4 times daily for those already diagnosed with heart disease.

Well, and there are a host of other nutrients proven to lower risk of cardiovascular disease.

The list is long but here is the quick version:

  • Polyphenols: Resveratrol,[28] de-alcolholyzed red wine,[29] purple grape juice,[30] red grape polyphenolic extract,[31] dark chocolate,[32] [33] and other plant-derived polyphenols[34] have been shown to safely reduce arterial wall inflammation,[35] increase nitric oxide (a vasodilator), and thereby lower both blood pressure and cardiovascular disease.

  • Omega 3 fatty acids (fish or fish oil) at 5 grams daily with EPA/DHA at a ratio of 3:2 lowers endothelial inflammation[36] [37] and at 3 to 4 grams daily it lowers the heart rate by 6 beats/minute and lowers endothelial inflammation.[38] [39] [40] [41] [42] [43]

  • Hawthorne berry mildly reduces systemic vascular resistance.[44] [45] [46]

  • Aged garlic (Kyolic) is clearly cardioprotective and there are multiple mechanisms for this.[47] [48] Clinical experience shows 600 mg twice daily reduces coronary artery plaque progression in people on statins[49] [50]

  • Berberine: effectively reduced cholesterol levels in hamsters fed a high-fat, high-cholesterol diet in an early study. A 2012 study[51] in humans found that 500 mg three times daily for 12 weeks was more effective in lowering cholesterol than ezetimibe.

  • Nattokinase from the Japanese natto bean is a natural clot buster and helps to keep optimal arterial blood flow.

  • Potassium: a high potassium diet of 5,000 mg daily[52] [53] is recommended (unless you have kidney failure) for optimal heart health and blood pressure.

So much for trying to tell us that “supplements and dietary interventions offer little (if any) protection against heart disease”! Don’t fall for such trickery!

To long term health,

Michael Cutler, M.D


[1] Khan SU, Khan MU, Riaz H, Valavoor S, Zhao D, Vaughan L, Okunrintemi V, Riaz IB, Khan MS, Kaluski E, Murad MH, Blaha MJ, Guallar E, Michos ED. Effects of Nutritional Supplements and Dietary Interventions on Cardiovascular Outcomes: An Umbrella Review and Evidence Map. Ann Intern Med. 2019 Jul 9. PubMed PMID: 31284304.


[3] Ibid

[4] Ornish D, Scherwitz LW, Billings JH, Brown SE, Gould KL, Merritt TA, Sparler S, Armstrong WT, Ports TA, Kirkeeide RL, Hogeboom C, Brand RJ. Intensive lifestyle changes for reversal of coronary heart disease. JAMA. 1998 Dec 16;280(23):2001-7. PubMed PMID: 9863851.


[6] Campbell TC, Parpia B, Chen J. Diet, lifestyle, and the etiology of coronary artery disease: the Cornell China study. Am J Cardiol. 1998 Nov 26;82(10B):18T-21T. PubMed PMID: 9860369.

[7] Key TJ, Thorogood M, Appleby PN, Burr ML. Dietary habits and mortality in 11,000 vegetarians and health conscious people: results of a 17 year follow up. BMJ. 1996 Sep 28;313(7060):775-9. PubMed PMID: 8842068.

[8] Grases F, Sanchis P, et al. Phytate (Myo-inositol hexakisphosphate) inhibits cardiovascular calcifications in rats. Frontiers in Bioscience January 1, 2006 (11)136-142

[9] A.A. López-González, F. Grases, P. Roca, B. Mari, M.T. Vicente-Herrero, and A. Costa-Bauzá. Journal of Medicinal Food. December 2008, 11(4): 747-752.

[10] Angel A. Lopez-Gonzalez, Felix Grases, et al. Protective effect of myo-inositol hexaphosphate (phytate) on bone mass in postmenopausal women. European Journal of Nutrition 2012, DOI: 10.1007/s00394-012-0377-6.

[11] Fodor D, Albu A, Poantă L, Porojan M. Vitamin K and vascular calcifications. Acta Physiol Hung. 2010 Sep;97(3):256-66.

[12] Wallin R, Schurgers L, Wajih N. Effects of the blood coagulation vitamin K as an inhibitor of arterial calcification. Thromb Res. 2008;122(3):411-7.

[13] Wallin R, Schurgers L, Wajih N. Effects of the blood coagulation vitamin K as an inhibitor of arterial calcification. Thromb Res. 2008;122(3):411-7.

[14] Geleijnse JM, Vermeer C, Grobbee DE, Schurgers LJ, Knapen MH, van der Meer IM, Hofman A, Witteman JC. Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the Rotterdam Study. J Nutr. 2004 Nov;134(11):3100-5.

[15] Gast GC, de Roos NM, Sluijs I, Bots ML, Beulens JW, Geleijnse JM, Witteman JC, Grobbee DE, Peeters PH, van der Schouw YT. A high menaquinone intake reduces the incidence of coronary heart disease. Nutr Metab Cardiovasc Dis. 2009 Sep;19(7):504-10.

[16] Higashi Y, Oshima T, Ozono R, Watanabe M, Matsuura H, Kajiyama G.Effects of L-arginine infusion on renal hemodynamics in patients with mild essential hypertension. Hypertension. 1995 Apr;25(4 Pt 2):898-902.

[17] Higashi Y, Oshima T, Watanabe M, Matsuura H, Kajiyama G. Renal response to L-arginine in salt-sensitive patients with essential hypertension. Hypertension. 1996 Mar;27(3 Pt 2):643-8.

[18] Siani A, Pagano E, Iacone R, Iacoviello L, Scopacasa F, Strazzullo P. Blood pressure and metabolic changes during dietary L-arginine supplementation in humans. Am J Hypertens. 2000 May;13(5 Pt 1):547-51.

[19] Campese VM, Amar M, Anjali C, Medhat T, Wurgaft A. Effect of L-arginine on systemic and renal haemodynamics in salt-sensitive patients with essential hypertension. J Hum Hypertens. 1997 Aug;11(8):527-32.

[20] Xu YJ, Arneja AS, Tappia PS, Dhalla NS. The potential health benefits of taurine in cardiovascular disease. Exp Clin Cardiol. 2008 Summer;13(2):57-65.

[21] Yamori Y, Taguchi T, Hamada A, Kunimasa K, Mori H, Mori M. Taurine in health and diseases: consistent evidence from experimental and epidemiological studies. J Biomed Sci. 2010 Aug 24;17 Suppl 1:S6.

[22] Vasdev S, Ford CA, Parai S, Longerich L, Gadag V.Dietary alpha-lipoic acid supplementation lowers blood pressure in spontaneously hypertensive rats. J Hypertens. 2000 May;18(5):567-73.

[23] Vasdev S, Ford CA, Parai S, Longerich L, Gadag V.Dietary alpha-lipoic acid supplementation lowers blood pressure in spontaneously hypertensive rats. J Hypertens. 2000 May;18(5):567-73.

[24] Li CJ, Zhang QM, Li MZ, Zhang JY, Yu P, Yu DM. Attenuation of myocardial apoptosis by alpha-lipoic acid through suppression of mitochondrial oxidative stress to reduce diabetic cardiomyopathy. Chin Med J (Engl). 2009 Nov 5;122(21):2580-6.

[25] Ghibu S, Richard C, Vergely C, Zeller M, Cottin Y, Rochette L. Antioxidant properties of an endogenous thiol: Alpha-lipoic acid, useful in the prevention of cardiovascular diseases. J Cardiovasc Pharmacol. 2009 Nov;54(5):391-8.

[26] Sudheesh NP, Ajith TA, Janardhanan KK, Krishnan CV. Palladium alpha-lipoic acid complex formulation enhances activities of Krebs cycle dehydrogenases and respiratory complexes I-IV in the heart of aged rats. Food Chem Toxicol. 2009 Aug;47(8):2124-8.

[27] Shecterle LM, Terry KR, St Cyr JA. The patented uses of D-ribose in cardiovascular diseases. Recent Pat Cardiovasc Drug Discov. 2010 Jun;5(2):138-42.

[28] Biala A, Tauriainen E, Siltanen A, Shi J, Merasto S, Louhelainen M, Martonen E, Finckenberg P, Muller DN, Mervaala E. Resveratrol induces mitochondrial biogenesis and ameliorates Ang II-induced cardiac remodeling in transgenic rats harboring human renin and angiotensinogen genes. Blood Press. 2010 Jun;19(3):196-205.

[29] Chiva-Blanch G, Urpi-Sarda M, Ros E, Arranz S, Valderas-Martínez P, Casas R, Sacanella E, Llorach R, Lamuela-Raventos RM, Andres-Lacueva C, Estruch R. Dealcoholized red wine decreases systolic and diastolic blood pressure and increases plasma nitric oxide: short communication. Circ Res. 2012 Sep 28;111(8):1065-8.

[30] Stein JH, Keevil JG, Wiebe DA, Aeschlimann S, Folts JD. Purple grape juice improves endothelial function and reduces the susceptibility of LDL cholesterol to oxidation in patients with coronary artery disease. Circulation. 1999 Sep 7;100(10):1050-5.

[31] Lekakis J, Rallidis LS, Andreadou I, Vamvakou G, Kazantzoglou G, Magiatis P, Skaltsounis AL, Kremastinos DT. Polyphenolic compounds from red grapes acutely improve endothelial function in patients with coronary heart disease. Eur J Cardiovasc Prev Rehabil. 2005 Dec;12(6):596-600.

[32] Grassi D, Lippi C, Necozione S, Desideri G, Ferri C. Short-term administration of dark chocolate is followed by a significant increase in insulin sensitivity and a decrease in blood pressure in healthy persons. Am J Clin Nutr. 2005 Mar;81(3):611-4.

[33] Taubert D, Roesen R, Schömig E. Effect of cocoa and tea intake on blood pressure: a meta-analysis. Arch Intern Med. 2007 Apr 9;167(7):626-34.

[34] Kanti Bhooshan Pandey and Syed Ibrahim Rizvi. Plant polyphenols as dietary antioxidants in human health and disease. Oxid Med Cell Longev. 2009 Nov-Dec; 2(5): 270–278. Online at:

[35] Layne J, Majkova Z, Smart EJ, Toborek M, Hennig B. Caveolae: a regulatory platform for nutritional modulation of inflammatory diseases. J Nutr Biochem. 2011 Sep;22(9):807-11.

[36] Alexander JW. Immunonutrition: the role of omega-3 fatty acids. Nutrition. 1998 Jul-Aug;14(7-8):627-33.

[37] Sagara M, Njelekela M, Teramoto T, Taguchi T, Mori M, Armitage L, Birt N, Birt C, Yamori Y. Effects of docosahexaenoic Acid supplementation on blood pressure, heart rate, and serum lipids in Scottish men with hypertension and hypercholesterolemia. Int J Hypertens. 2011 Mar 8;2011:809198.

[38] Mori TA, Bao DQ, Burke V, Puddey IB, Beilin LJ. Docosahexaenoic acid but not eicosapentaenoic acid lowers ambulatory blood pressure and heart rate in humans. Hypertension. 1999 Aug;34(2):253-60.

[39] Alexander JW. Immunonutrition: the role of omega-3 fatty acids. Nutrition. 1998 Jul-Aug;14(7-8):627-33.

[40] Sagara M, Njelekela M, Teramoto T, Taguchi T, Mori M, Armitage L, Birt N, Birt C, Yamori Y. Effects of docosahexaenoic Acid supplementation on blood pressure, heart rate, and serum lipids in Scottish men with hypertension and hypercholesterolemia. Int J Hypertens. 2011 Mar 8;2011:809198.

[41] Toft I, Bønaa KH, Ingebretsen OC, Nordøy A, Jenssen T. Effects of n-3 polyunsaturated fatty acids on glucose homeostasis and blood pressure in essential hypertension. A randomized, controlled trial. Ann Intern Med. 1995 Dec 15;123(12):911-8.

[42] Ueshima H, Stamler J, Elliott P, Chan Q, Brown IJ, Carnethon MR, Daviglus ML, He K, Moag-Stahlberg A, Rodriguez BL, Steffen LM, Van Horn L, Yarnell J, Zhou B; INTERMAP Research Group. Food omega-3 fatty acid intake of individuals (total, linolenic acid, long-chain) and their blood pressure: INTERMAP study. Hypertension. 2007 Aug;50(2):313-9.

[43] Park Y, Oh SH, Rhee MY. Association between 24-hour ambulatory blood pressure and erythrocyte n-3 polyunsaturated fatty acids in Korean subjects with hypertension. Nutr Res. 2010 Dec;30(12):807-14

[44] Schussler M, Holzl J, Fricke U. Myocardial effects of flavonoids from Crataegus species. Arzneimittelforschung 1995 45(8):842-5.

[45] Bahorun, T. Antioxidant activities of Crataegus monogyna extracts. Planta Medica 1994 60:323-8

[46] Busse W. Standardized Crataegus extract clinical monograph. Q Rev Nat Med 1996 189-97.

[47] Khatua TN, Adela R, Banerjee SK. Garlic and cardioprotection: insights into the molecular mechanisms. Can J Physiol Pharmacol. 2013 Jun;91(6):448-58.

[48] Ginter E, Simko V. Garlic (Allium sativum L.) and cardiovascular diseases. Bratisl Lek Listy. 2010;111(8):452-6.

[49] Rai SK, Sharma M, Tiwari M. Inhibitory effect of novel diallyldisulfide analogs on HMG-CoA reductase expression in hypercholesterolemic rats: CREB as a potential upstream target. Life Sci. 2009 Jul 31;85(5-6):211-9.

[50] Presentation by Mark Houston, M.D. (cardiologist) at the American Academy of Anti-aging Medicine fellowship module II.

[51] Gonnelli S, Caffarelli C, Stolakis K, Cuda C, Giordano N, Nuti R. Efficacy and Tolerability of a Nutraceutical Combination (Red Yeast Rice, Policosanols, and Berberine) in Patients with Low-Moderate Risk Hypercholesterolemia: A Double-Blind, Placebo-Controlled Study. Curr Ther Res Clin Exp. 2014 Nov

15;77:1-6. PubMed PMID: 26649075.

[52] Personal notes taken from the American Academy of Anti-aging Medicine fellowship module II training, 2012.

[53] Poorolajal J, Zeraati F, Soltanian AR, Sheikh V, Hooshmand E, Maleki A. Oral potassium supplementation for management of essential hypertension: A meta-analysis of randomized controlled trials. PLoS One. 2017 Apr 18;12(4):e0174967. eCollection 2017. PubMed PMID: 28419159; PubMed Central PMCID: PMC5395164.

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