Major NIH Nutrition Trials on Diet & Health Ignored

Results of long-term, randomized, controlled, clinical trials on some 80,000 people never considered in formulating the US Dietary Guidelines.

Dr. Jay Bhattacharya, Director of the National Institutes of Health (NIH), stated upon taking office that his top priority is to determine the causes of chronic diseases and how to reverse them. “We have to understand why our children are facing shorter lives than we are,” he urged at the White House at the release of the MAHA Commission Report in May.

Yet, as he commands the nation’s premier research institution with an annual budget of $48 billion, Bhattacharya is surely wondering: Why has an agency that’s spent trillions of dollars since its founding in 1948—then with a mission to fight heart disease—not made more progress so far? Not only is heart disease still the leading cause of death in the U.S., according to the CDC, but rates of other chronic diseases have skyrocketed during the agency’s 77-year history. How come we still know so little?

I’m surprised more nutrition experts haven’t challenged the very premise of Bhattacharya’s goal, since they often tell us that they already know how to prevent these diseases. It’s “simple,” not complicated—pretty obvious, in fact, as Nutrition Goddess Marion Nestle, NYU Professor Emeritus, often drills down for us. A healthy diet is one high in fruits, vegetables, whole grains, beans and legumes, fish and seafood, nuts, and seeds, while lower in sugar, red and processed meats, and ultra-processed foods. Additionally, she and most experts recommend low-fat dairy products over the full-fat variety and seed oils over butter.

This is The Diet, endorsed by nearly all experts and health organizations. Harvard agrees; Tufts agrees; Stanford agrees; the Mayo Clinic agrees; the American Heart Association, the American Academy of Pediatrics, the American Cancer Society, and yes, the U.S. Dietary Guidelines of Americans—our nation’s top nutrition policy--all agree. Everyone agrees.

This checkerboard of faces once graced the homepage of the True Health Initiative (THI), a “plant-predominant” advocacy group known for its aggressive tactics, such as demanding retraction of papers before they’re even published. You might recognize some of these headshots—Harvard nutrition leader Walter Willett; Sam Kass, former NBC Senior Food Analyst and White House chef under the Obamas, who now runs a food investment fund; Blue Zones empresario Dan Beutner, and leaders from the plant-based American College of Lifestyle Medicine. There are members from Johns Hopkins, Stanford, Tufts, and other leading universities. The magnitude of all their degrees and prestigious institutions cannot fail to convey the authority of the dominant narrative on diet and health. “Many experts…One voice,” says THI.

Unluckily for the agree-ers, however, the new NIH-in-chief has expressed skepticism for what he calls “group think,” in which a field of science has coalesced around single, dominant viewpoints and discourages alternatives. The tools for maintaining discipline within a scientific field are numerous. Its leaders control invitations to conferences, access to research funding, fellowships, leadership positions, and awards; they gatekeep who gets their papers published in top journals. These spoils are distributed to those who conform to mainstream views, while challengers see them fade away. I’ve seen this duality firsthand, having co-authored papers with top nutrition experts—a relative breeze—and also ventured out on my own, with a prominent BMJ cover story challenging the U.S. Dietary Guidelines that was then subject to the largest retraction effort in modern history. By necessity, the rules must be essentially unyielding to preserve discipline in a field of science.

Enforcement has long been strict within the field of nutrition science. Since the early 1960s, the central idea that saturated fat and cholesterol cause heart disease, called the “diet-heart hypothesis,” was adopted by leading nutrition experts of the day, including those at the American Heart Association and NIH. This hypothesis meant cutting back on meat, full-fat dairy, eggs, and butter, which necessitated a shift to seed oils, fruits, vegetables, and grains—the eventual components of The Diet.

Critics who spoke out against the diet-heart hypothesis saw their careers virtually ruined. For instance, when the once-prominent NIH-funded scientist George Mann from Vanderbilt University, a director of the famous Framingham Heart Study, went public with research findings contrary to the hypothesis in the 1970s, he found his NIH research grant canceled. Mann had spent two years collecting food-consumption data from 1,000 Framingham subjects, with the conclusion that when it came to saturated fats and coronary heart disease, “No relationship found.”

“That went over like a wet blanket with my superiors at NIH,” Mann told me, “because it was contrary to what they wanted us to find.” His results lay in an NIH basement for nearly a decade. (To withhold scientific information “is a form of cheating,” Mann lamented.) And even when the findings eventually came out in 1968, they were so deeply buried that a researcher has to dig through 28 volumes to find the news that variations in serum cholesterol levels could not be traced back to the amount or type of fat eaten.

Mann is just one of many stories. Another NIH researcher, Ivan Frantz, who directed one of the largest and well-controlled studies on a diet low in saturated fat and cholesterol—the Minnesota Coronary Survey—did not publish his results for 16 years. In effect, he self-censored. “There was nothing wrong with our study,” he told the journalist Gary Taubes in an interview. “We were just disappointed in the way it came out.” (Decades later, Frantz’s son found the original computer tapes from the study in his father’s basement which, when analyzed by an NIH researcher, revealed the never-published finding that the more the 9,057 men and women in the study lowered their cholesterol, the more likely they were to die from heart disease.)

Today, accusations are flying at NIH about censorship and suppression of science, as if the institution has a long, pristine record that the current leadership is uniquely tainting. Yet, nothing could be further from the truth. In nutrition research, the rejection and even suppression of contrary findings has been the norm. Bhattacharya appears committed to reversing this record. (Consider the multiple layers of irony in the fact that even as Bhattacharya’s critics lambast him, they are still asking him to double the NIH research budget on nutrition, from $4 billion to $8 billion, for questions that they believe have already been answered.)

Below is a list of NIH trials, stunning in their scope and ambition, that tested some version of the diet-heart hypothesis, with “disappointing” findings that have largely been ignored. The NIH conducted randomized, controlled clinical trials—the most rigorous type of study—on nearly 80,000 people, most lasting 4-7 years. And if anything, these trials conclude that key aspects of The Diet cannot be shown to prevent chronic diseases of any kind.

Specifically, a diet low in saturated fat and cholesterol and/or a diet low in total fat while higher in fruits, vegetables, and grains does not protect against obesity, diabetes, heart disease, or any type of cancer.

These trials, from the 1960s through the 1990s, marked a golden age of NIH nutrition research.

Major NIH-Funded Trials on the Dietary Guidelines

(Not a comprehensive list)
Total number of people tested: 79,840
Duration of studies: 7 out of 9 studies are >1 year; The largest studies are 4-9 years.
Note: A fully referenced list of these studies is available HERE.

Los Angeles Veteran’s Trial
Summary: A diet that replaced saturated fat with vegetable oils successfully lowered cases of heart disease yet did not reduce total mortality. The men on the seed oil diet died at higher rates of cancer.
Study: An 8-year randomized, controlled clinical trial on 846 men in a Los Angeles Veterans home tested the hypothesis that a diet reduced in saturated fats and cholesterol can prevent heart disease. The intervention diet served 40% of calories as fat from seed oils: corn, soybean, safflower, and cottonseed oils. Further, this diet served seed-oil “filled” milk, imitation ice cream, margarine, non-meat sausages, and seed-oil-filled cheeses. The control diet also contained 40% of calories as fat but from animal sources (butter, lard, tallow).
Results (1969): Total cholesterol was successfully lowered by 12.7% more in the intervention group compared to controls. Only 48 men on the seed oil diet died from heart disease compared to 70 in the saturated fat group. However, the total rates of deaths from all causes for the two groups were the same. Further, 31 of the subjects on the seed oil diet died of cancer, compared to only 17 of the controls.
Lay summary: A diet low in saturated fats and high in seed oils had no effect on mortality. Men on the diet high in seed oils died at higher rates from cancer.

Multiple Risk Factor Intervention Trial Research Group (MRFIT) Trial
Summary: A large and long-term nutrition study found that a diet low in saturated fat and cholesterol increased rates of death and lung cancer in men compared to controls.
Study: A 7+-year randomized, controlled clinical trial on 12,866 men with high total cholesterol tested the hypothesis that heart disease could be prevented by a multifactorial intervention, including counseling to quit smoking, medication to lower blood pressure, and a diet reduced in saturated fats and cholesterol. Begun in 1973, MRFIT was at the time one of the biggest and most ambitious medical experiments ever performed, involving 28 medical centers nationwide and costing $115 million.
Results (1982): Although men in the intervention group had been spectacularly successful in changing their diets, quitting smoking, and reducing their blood pressure, they died at slightly higher rates than the controls. At the 16-year follow-up to the study in 1997, the treatment group was found to have higher rates of lung cancer even though 21% of them had quit smoking, compared to only 6% of the controls.
Lay summary: Men following a diet low in saturated fat and cholesterol (many of whom also quit smoking) died at a higher rate than the control group. They also died at higher rates from lung cancer.

Minnesota Coronary Survey
Summary: The largest-ever test of the “diet-heart hypothesis” found that saturated fats have no effect on heart disease, cardiovascular mortality, or total mortality. In addition, researchers later found that the more the subjects lowered their cholesterol, the higher their risk of death.
Study: A 4.5-year randomized, controlled clinical trial on 9,057 men and women in six Minnesota state mental hospitals and one nursing home tested the hypothesis that a diet reduced in saturated fat can prevent heart disease. An intervention diet with 9% of calories as saturated fat was compared to one with 18% (the control group).
Results (1989, 2016): Total cholesterol was successfully lowered by 13.8%, yet the authors reported that “[f]or the entire study population, no differences between the treatment and control groups were observed for cardiovascular events, cardiovascular deaths, or total mortality”. The authors did not publish the study for 16 years, explaining to a journalist that there was “nothing wrong” with the study but that they were “so disappointed in the way it turned out”. Seventeen years later, unpublished data discovered in the project leader’s basement was analyzed by NIH researchers, who found the following: for each 30 mg/dL reduction in serum cholesterol by the men, there was a 22% higher risk of death.
Lay summary: A diet low in saturated fats and cholesterol did not reduce cardiovascular events or mortality of any kind. The more the men lowered their cholesterol, the more likely they were to die.

Dietary Alternatives Study
Summary: A diet low in total fat, saturated fat and cholesterol had mixed results on cardiovascular risk and no beneficial effect on weight, type 2 diabetes, or blood pressure.
Study: A 1-year randomized, controlled clinical trial on 531 male Boeing employees with heart disease tested the hypothesis that diets <7% of calories from saturated fat and <30% from total fat (four diets ranging from 18-30% of calories from fat) can prevent the progression of heart disease.
Results (1997): The diet had conflicting results for heart disease. It lowered LDL-cholesterol (LDL-C) in the intervention group compared to controls, a potential sign of reduced cardiovascular risk, yet the diet also decreased HDL-cholesterol (HDL-C) and dramatically increased triglycerides (by 20-40% in two groups), which are powerful signs of increasing cardiovascular risk. The study also reported that weight loss, blood pressure, and the risk of type 2 diabetes (insulin concentrations and blood sugar levels) did not improve in three groups compared to controls.

beFIT Study
Summary: A diet low in total fat, saturated fat, and cholesterol does not clearly protect against heart disease.
Study: A 6-month randomized, controlled clinical trial on a diet with <7% of calories as saturated fat, <30% from total fat, and <200 mg/d dietary cholesterol tested whether this intervention could reduce the risk of heart disease. Subjects were 178 female and 231 male (409 total) Boeing employees with “hypercholesterolemia,” i.e., adverse cholesterol measures (LDL-cholesterol and triglycerides).
Results (1997): HDL-cholesterol significantly decreased in women (−6.4% and −4.7%) but not in men (−1.3% and −2.7%). Declining HDL-C is a sign of worsening heart disease risk. By contrast, LDL-cholesterol decreased by 8.6%, which could be a positive result. Overall, these are conflicting results. A one-year follow-up report found that women with hypercholesterolemia had significantly worse outcomes for HDL-C, with a decrease of 16.7% compared to an increase of 0.5% among matched men. The implication is that the low-fat diet disproportionately increases the risk of heart disease for women.

Women’s Health Initiative (WHI)
Summary: A diet high in fruits and vegetables and low in fat, saturated fat, and cholesterol does not prevent obesity, type 2 diabetes, heart disease, or cancer.
Study: An 8-year randomized, controlled clinical trial on nearly 49,000 women tested the hypothesis that the Dietary Guidelines, reduced in fat, saturated fat, and cholesterol while higher in fruits and vegetables, can prevent cancer (primary outcome), heart disease, obesity, and diabetes. This was the largest nutrition trial ever conducted worldwide, costing $725 million.
Results (2006): The diet did not prevent heart disease, type 2 diabetes, breast cancer, colorectal cancer, ovarian cancer or endometrium cancer. After eight years, the women on the diet weighed, on average, only two pounds less than the controls.

Polyp Prevention Trial
Summary: A low-fat diet low in fat and high in fruits, vegetables, and fiber does not prevent colorectal cancer.
Study: A 4-year randomized, controlled clinical trial on 2,079 men and women with confirmed colorectal adenomas tested the hypothesis that a diet low in fat (20% of calories) and high in fruits, vegetables, and fiber (18 g of dietary fiber per 1,000 calories) can prevent the recurrence of adenomatous polyps of the large bowel, which are precursors of most colorectal malignancies (colorectal cancer).
Results (2000, 2007): In 2000, the authors reported in the New England Journal of Medicine that “adopting a diet that is low in fat and high in fiber, fruits, and vegetables does not influence the risk of recurrence of colorectal adenomas”. Eight years later, a follow-up study reported “no effect of a low-fat, high-fiber, high-fruit, and -vegetable diet on adenoma recurrence eight years after randomization.”

Dietary Guidelines Trial
Summary: A well-controlled clinical trial found that the US Dietary Guidelines did not outperform a diet high in sugar and refined grains. Compared to these controls, the guidelines diet did not improve markers for heart disease or type 2 diabetes, with the exception of a reduction in systolic blood pressure.
Study: An eight-week randomized, controlled clinical trial on 52 women, in which all food was provided, tested the U.S. Dietary Guidelines (DGA) against a “typical American diet” (TAD), higher in refined grains, saturated fat, and sugar. The TAD women were told to consume 3.5 additional servings of refined grains per day, including lemon cheesecake and candy, including “Jelly Bellies,” as “all-day condiments.”
Results (2018): The DGA women achieved the goal of closely following the guidelines, scoring 98 out of 100 on the Healthy Eating Index (HEI), a measure of DGA adherence. The TAD women, by contrast, scored 65-69 on HEI. The study found no significant difference between the intervention and control groups for total cholesterol, HDL-C, LDL-C, triglycerides, diastolic blood pressure, fasting insulin, glucose, oral glucose tolerance, and insulin resistance measures. The authors found only one superior outcome in the DGA group: a reduction in systolic blood, which they reported as “∼−9 mm Hg.” However, the results from the paper itself showed only a 6.3 mm Hg reduction. (This was still better than the -2.4 mm Hg reduction in the TAD group.)

The Action for Health in Diabetes (Look AHEAD) Trial
Summary: A diet low in fat and saturated fat does not prevent heart disease or obesity.
Study: A $200 million randomized, controlled clinical trial on ~5,000 subjects with overweight/obesity and type 2 diabetes, was intended to last 9-11 years. The trial tested the idea that a diet reduced in fat and saturated fat can prevent heart disease and help people lose weight.
Results (2021): The study was stopped early due to “futility,” as it showed no benefit for cardiovascular disease, the primary outcome. This result was “unexpected and disappointing to many,” according to the study’s final paper. The low-fat diet also resulted in worse outcomes for body composition (weight), bone density, and frailty fractures compared to the control group.

DELTA 1
Summary: Diets low in total fat and saturated fat lowered LDL-cholesterol yet also decreased HDL-cholesterol, increased triglycerides (in the case of Step 1), and also increased Lp(a). Overall, more markers of heart disease worsened than improved.
Study: A multicenter, randomized, crossover-design trial on 103 healthy adults 22 to 67 years old. There were 46 men and 57 women, of whom 26 were black, 18 were postmenopausal women, and 16 were men >= 40 years old. Three diets were compared: an American Heart Association “Step 1” diet (28.6% calories fat and 9.0% calories saturated fats), a “Low-Sat” diet (25.3% cal fat and 6.1% cal saturated fats), and an “average American diet (AAD)” (34.3% cal fat and 15.0% cal SFA). All meals and snacks, except Saturday dinner, were prepared and served by the research centers; thus, the study was highly controlled.
Results (1998): Compared with AAD, total cholesterol in the whole group fell 5% on Step 1 and 9% on Low-Sat diets. LDL-cholesterol was 7% lower on Step 1 and 11% lower on Low-Sat than on the AAD. HDL-cholesterol fell 7% on Step 1 and 11% on Low-Sat compared to AAD. Plasma triglyceride levels increased by 9% between AAD and Step 1 but did not increase further from Step 1 to Low-Sat. Surprisingly, plasma Lp(a) concentrations increased in a stepwise fashion as SFA was reduced.

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These trials were funded, intending to inform our nation’s nutrition policy, the US Dietary Guidelines for Americans (DGA). Yet, as I reported in a BMJ cover story in 2015, the trials on saturated fats had “never been systematically reviewed by any of the dietary guideline committees.” Subsequent DGA scientific reviews, in 2020 and 2025, also did not review these trial results. (My review of the 2020 DGA process was published in Nutrients, with co-authors that include former DGA Advisory Committee members; I published my 2025 review on Substack).

How and why these important research findings have been so long ignored is a complex story, but the anecdotes above, about George Mann and Ivan Frantz, provide a glimpse into the long-time groupthink that has dominated this field of science.

Due to this lamentable history, restrictions on saturated fat remain; the low-fat diet is still enshrined in USDA feeding assistance programs, including school lunches; and the guidelines still recommend diets “lower in cholesterol,” despite all the rigorous, ignored evidence to the contrary.

Going forward, the NIH should acknowledge that certain scientific ideas in nutrition—including the diet-heart hypothesis--have been tested enough. Disappointing as the results may be, experts need to reckon with these findings and move beyond this narrative that has dominated our understanding of nutrition for decades, to new, more promising nutritional approaches for preventing and reversing the chronic diseases that afflict far too many of us.

To my readers: I apologize sincerely for not posting recently; I was on vacation last week, but otherwise, my time has been consumed by providing information to policymakers in a position to change our nutrition guidance. I promise to step up these posts going forward! My grateful thanks to you all for your patience and support.

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