Tag Archives: cardiovascular disease

Eat Nuts to Improve Your Blood Lipids and Reduce Risk of Cardiovascular Disease

Posted on September 9, 2015 | Comments Off

Cashews fresh off the tree. They’re actually fruits, not nuts.

Most of the diets I recommend to my patients include nuts because they are so often linked to improved cardiovascular health in scientific studies. Walnuts are associated with reduced risk of type 2 diabetes in women, and established type 2 diabetics see improved blood sugar control and lower cholesterols when adding nuts to their diets.

Nut consumption lowers total and LDL cholesterol levels, and if triglycerides are elevated, nuts lower them, too. Those changes would tend to reduce heart disease.

Conner Middelmann-Whitney has a good nutty article at Psychology Today.

Steve Parker, M.D.

Reference: Joan Sabaté, MD, DrPH; Keiji Oda, MA, MPH; Emilio Ros, MD, PhD. Nut Consumption and Blood Lipid Levels: A Pooled Analysis of 25 Intervention Trials. Archives of Internal Medicine, 2010, Vol. 170 No. 9, pp 821-827. Abstract:

Background Epidemiological studies have consistently associated nut consumption with reduced risk for coronary heart disease. Subsequently, many dietary intervention trials investigated the effects of nut consumption on blood lipid levels. The objectives of this study were to estimate the effects of nut consumption on blood lipid levels and to examine whether different factors modify the effects.

Methods: We pooled individual primary data from 25 nut consumption trials conducted in 7 countries among 583 men and women with normolipidemia and hypercholesterolemia who were not taking lipid-lowering medications. In a pooled analysis, we used mixed linear models to assess the effects of nut consumption and the potential interactions.

Results: With a mean daily consumption of 67 g of nuts [about 2 ounces or 2 palms-ful], the following estimated mean reductions were achieved: total cholesterol concentration (10.9 mg/dL [5.1% change]), low-density lipoprotein cholesterol concentration (LDL-C) (10.2 mg/dL [7.4% change]), ratio of LDL-C to high-density lipoprotein cholesterol concentration (HDL-C) (0.22 [8.3% change]), and ratio of total cholesterol concentration to HDL-C (0.24 [5.6% change]) (P < .001 for all) (to convert all cholesterol concentrations to millimoles per liter, multiply by 0.0259). Triglyceride levels were reduced by 20.6 mg/dL (10.2%) in subjects with blood triglyceride levels of at least 150 mg/dL (P < .05) but not in those with lower levels (to convert triglyceride level to millimoles per liter, multiply by 0.0113). The effects of nut consumption were dose related, and different types of nuts had similar effects on blood lipid levels. The effects of nut consumption were significantly modified by LDL-C, body mass index, and diet type: the lipid-lowering effects of nut consumption were greatest among subjects with high baseline LDL-C and with low body mass index and among those consuming Western diets.

Conclusion: Nut consumption improves blood lipid levels in a dose-related manner, particularly among subjects with higher LDL-C or with lower BMI.

Comments Off on Eat Nuts to Improve Your Blood Lipids and Reduce Risk of Cardiovascular Disease

Posted in Coronary Heart Disease, Heart Disease, Nuts

Tagged blood lipids, cardiovascular disease, nuts

Dietary Cholesterol Unrelated to Cardiovascular Disease!

Posted on August 18, 2015 | Comments Off

…according to this article at American Journal of Clinical Nutrition.

Heart attack on a plate? Think again

This is quite contrary to the party line spread by public health authorities for the last 40 years.

Enjoy your eggs! (If you can afford them.)

Comments Off on Dietary Cholesterol Unrelated to Cardiovascular Disease!

Posted in Coronary Heart Disease, Heart Disease

Tagged cardiovascular disease, dietary cholesterol, heart disease

Still Taking Fish Oil Supplements? Think Again

Posted on October 30, 2014 | 2 comments

Salmon is one the the cold-water fatty fish loaded with omega-3 fatty acids

I’ve been sitting on this research report a few years, waiting until I had time to dig into it. That time never came. The full report is free online (thanks, British Medical Journal!). I scanned the full paper to learn that nearly all the studies in this meta-analysis used fish oil supplements, not the cold-water fatty fish the I recommend my patients eat twice a week. If you’re taking fish oil supplements on your doctor’s advice, don’t stop without consulting her.

Here’s the abstract:

Objective: To review systematically the evidence for an effect of long chain and shorter chain omega 3 fatty acids on total mortality, cardiovascular events, and cancer.

Data sources: Electronic databases searched to February 2002; authors contacted and bibliographies of randomised controlled trials (RCTs) checked to locate studies.

Review methods Review of RCTs of omega 3 intake for 3 6 months in adults (with or without risk factors for cardiovascular disease) with data on a relevant outcome. Cohort studies that estimated omega 3 intake and related this to clinical outcome during at least 6 months were also included. Application of inclusion criteria, data extraction, and quality assessments were performed independently in duplicate.

Results: Of 15 159 titles and abstracts assessed, 48 RCTs (36 913 participants) and 41 cohort studies were analysed. The trial results were inconsistent. The pooled estimate showed no strong evidence of reduced risk of total mortality (relative risk 0.87, 95% confidence interval 0.73 to 1.03) or combined cardiovascular events (0.95, 0.82 to 1.12) in participants taking additional omega 3 fats. The few studies at low risk of bias were more consistent, but they showed no effect of omega 3 on total mortality (0.98, 0.70 to 1.36) or cardiovascular events (1.09, 0.87 to 1.37). When data from the subgroup of studies of long chain omega 3 fats were analysed separately, total mortality (0.86, 0.70 to 1.04; 138 events) and cardiovascular events (0.93, 0.79 to 1.11) were not clearly reduced. Neither RCTs nor cohort studies suggested increased risk of cancer with a higher intake of omega 3 (trials: 1.07, 0.88 to 1.30; cohort studies: 1.02, 0.87 to 1.19), but clinically important harm could not be excluded.

Conclusion: Long chain and shorter chain omega 3 fats do not have a clear effect on total mortality, combined cardiovascular events, or cancer.

Steve Parker, M.D.

Reference: Hooper, Lee et al. Risks and benefits of omega 3 fats for mortality, cardiovascular disease, and cancer: systematic review. BMJ 2006;332:752-760 (1 April), doi:10.1136/bmj.38755.366331.2F (published 24 March 2006).

2 Comments

Posted in Diet-Heart Hypothesis, Heart Disease, Supplements

Tagged cardiovascular disease, cold-water fatty fish, fish oil, fish oil supplements, heart disease, omega-3 fatty acids, salmon

Heart-Healthy Lifestyle Also Cuts Cancer Risk By Half

Posted on March 19, 2013 | 1 comment

…according to a report in MedPageToday.

I’m still not convinced that severe sodium restriction is necessary or even possible for most people

The American Heart Association has published guidelines aiming to reduce premature death and illness caused by cardiovascular diseases such as heart attacks, high blood pressure, and strokes.

The guidelines focus on seven factors critical to cardiovascular health:

smoking
blood sugar
blood pressure
physical activity
total cholesterol
body mass index (BMI)
ideal diet

Using data from the Atherosclerosis Risk In Communities study (almost two decades’ follow-up), researchers found that those who maintained goals for six or seven of the American Heart Association critical factors had a 51% lower risk of cancer compared with those meeting no goals.

For detailed information about the specific goals, click here.

As you might expect, I was curious about what the American Heart Association considered a heart-healthy diet. I quote the AHA summary:

The recommendation for the definition of the dietary goals and metric, therefore, is as follows: “In the context of a diet that is appropriate in energy balance, pursuing an overall dietary pattern that is consistent with a DASH [Dietary Approaches to Stop Hypertension]-type eating plan, including but not limited to:

Fruits and vegetables: ≥ 4.5 cups per day
Fish: ≥ two 3.5-oz servings per week (preferably oily fish)
Fiber-rich whole grains (≥ 1.1 g of fiber per 10 g of carbohydrate): ≥ three 1-oz-equivalent servings per day
Sodium: < 1500 mg per day
Sugar-sweetened beverages: ≤ 450 kcal (36 oz) per week

Intake goals are expressed for a 2000-kcal diet and should be scaled accordingly for other levels of caloric intake. For example, ≤ 450 calories per week represents only up to one quarter of discretionary calories (as recommended) coming from any types of sugar intake for a 2000-kcal diet.

Diet recommendations are more complicated than that; read the full report for details. Only 5% of study participants ate the “ideal diet.” The Mediterranean diet easily meets four out of five of those diet goals; you’d have to be extremely careful to reach the sodium goal on most any diet.

Cardiovascular diseases and cancer are among the top causes of death in Western societies. Adhering to the guidelines above may kill two birds with one stone.

Steve Parker, M.D.

1 Comment

Posted in Cancer, Coronary Heart Disease, Diet-Heart Hypothesis, Exercise, Heart Disease, High Blood Pressure

Tagged American Heart Association, cancer, cardiovascular disease, diet, heart-healthy diet, Mediterranean diet, stroke

High Calcium Intake Linked to Higher Risk of Death In Swedish Women

Posted on March 18, 2013 | Comments Off

Six of every 10 middle-aged and older women in the U.S. are taking calcium supplements, hoping to keep their bones strong and thereby avoid osteoporotic fractures of the hip, spine, and wrist. A new study in the British Medical Journal suggests that high calcium consumption, whether from food or supplements, increases the risk of death.

The researchers wrote:

In this study of women in the Swedish mammography cohort, a high calcium intake (>1400 mg/day) was associated with an increased rate of mortality, including death from cardiovascular disease. The increase was moderate with a high dietary calcium intake without supplement use, but the combination of a high dietary calcium intake and calcium tablet use resulted in a more pronounced increase in mortality. For most women with lower intakes we observed only modest differences in risk.

Comments Off on High Calcium Intake Linked to Higher Risk of Death In Swedish Women

Posted in Uncategorized

Tagged calcium, calcium supplements, cardiovascular disease, death, dietary calcium, osteoporosis

Huge U.S. Study Confirms Health and Longevity Benefits of the Mediterranean Diet

Posted on September 3, 2012 | Comments Off

This is a reprint of the very first blog post I ever did, from December 24, 2007, at my old Advanced Mediterranean Diet Blog.

We now have results of the first U.S. study on mortality and the Mediterranean dietary pattern. 380,000 people, aged 50-71, were surveyed on their dietary habits and scored on their conformity to the Mediterranean diet. They were visited again 10 years later. As you would expect, some of them died. 12,105 to be exact: 5985 from cancer, 3451 from cardiovascular disease, 2669 from other causes. However, the people with the highest adherence to the Mediterranean diet had better survival overall, and specifically better odds of avoiding death from cardiovascular disease and cancer. Compared to the people with low conformity to the Mediterranean diet, the high conformers were 15-20% less likely to die over the 10 years of the study. The study authors, funded by the National Institutes of Health, noted eight similar studies in Europe and one in Australia with similar results.

Nothing to do with this post…I just like this picture

Once again, my promotion of the Mediterranean diet is vindicated by the scientific literature. I’m not aware of any other diet that can prove anywhere near this degree of health benefit. If you are, please share.

Steve Parker, M.D.

Reference: Mitrou, Panagiota N., et al. Mediterranean Dietary Pattern and Prediction of All-Cause Mortality in a US Population, Archives of Internal Medicine, 167 (2007): 2461-2468.

Comments Off on Huge U.S. Study Confirms Health and Longevity Benefits of the Mediterranean Diet

Posted in Cancer, Heart Disease, Longevity

Tagged cancer, cardiovascular disease, healthy diet, longevity, Mediterranean diet, mortality

Fat or Fit: Which Is Healthier?

Posted on August 25, 2012 | Comments Off

Men live longer if they improve or maintain their fitness level over time, according to research out of the Cooper Clinic in Dallas, Texas. Part of that improved longevity stems from reduced risk of death from cardiovascular disease such as heart attack and stroke.

Compared with men who lose fitness with aging, those who maintained their fitness had a 30% lower risk of death; those who improved their fitness had a 40% lower risk of death. Fitness was judged by performance on a maximal treadmill exercise stress test.

Body mass index over time didn’t have any effect on all-cause mortality but was linked to higher risk of cardiovascular death. The researchers, however, figured that losses in fitness were the more likely explanation for higher cardiovascular deaths. In other words, as men age, it’s more important to maintain or improve fitness than to lose excess body fat or avoid overweight.

Steve Parker, M.D.

Reference: Lee, Duck-chul, et al. Long-term effects of changes in cardiorespiratory fitness and bodly mass index on all-cause and cardiovascular disease mortality in men. Circulation, 124 (2011): 2,483-2,490

Comments Off on Fat or Fit: Which Is Healthier?

Posted in Exercise, Heart Disease, Longevity, Stroke

Tagged body mass index, cardiovascular disease, Cooper Clinic, fitness, heart attack, longevity, stroke

Huge U.S. Study Confirms Health and Longevity Benefits of the Mediterranean Diet

Posted on July 27, 2012 | 4 comments

This is a reprint of my very first blog post, from December 24, 2007, at the old Advanced Mediterranean Diet Blog.

Reference: Mitrou, Panagiota N., et al. Mediterranean Dietary Pattern and Prediction of All-Cause Mortality in a US Population, Archives of Internal Medicine, 167 (2007): 2461-2468.

4 Comments

Posted in Cancer, Heart Disease, Longevity

Tagged cardiovascular disease, longevity, Mediterranean diet

Health Benefits of Dark Chocolate

Posted on June 4, 2012 | Comments Off

Theobroma cacao, the cocoa tree, has been cultivated in Central and South America for over 3000 years. Cocoa is derived from the tree’s seed, also known as the cocoa bean.

Chocolate is a product of the processed cocoa bean. Sweet chocolate is chocolate combined with sugar. Milk chocolate is sweet chocolate combined with milk powder or condensed milk. Dark chocolate typically has no added dairy products, has at least 65% cocoa content, and has much more of the potentially healthy chemicals from the cocoa bean as compared with milk chocolate. White chocolate is cocoa butter (aka cacao fat), milk solids, and sugar without the cocoa solids or mass; in many countries it is not considered chocolate.

It’s been a little over 10 years since we first read in a medical journal about cocoa and chocolate as potential sources of antioxidants for health. What have we learned since then?

Phytochemicals are chemicals produced by plants, and there are hundreds of thousands of them. Polyphenols are a subset of phytochemicals. Flavonoids, with strong antioxidant properties, are a subset of polyphenols. And a subset of flavonoids, called flavonols, have particularly potent biological effects in humans. Prominent flavonols in dark chocolate are flavan-3-ol, catechin, and epicatechin. Also metabolically active are proanthocyanidins, which are polymeric condensation products of flavan-3-ol.

Are you bored yet? Have I convinced you of my authority on the subject? Say yes, or I’ll keep going! [Please say yes: I’m boring myself!]

Note that some chocolate manufacturers process the cocoa beans to remove some of the polyphenols, which reduces bitterness or pungency.

Other rich sources of flavonols are wine, tea, and various fruits and berries.

How could dark chocolate, especially its flavonoids, be healthful?

Flavonoids are antioxidants that protect from injury caused by free radicals
Enhanced nitric oxide production, leading to relaxation of arteries (vasodilation), leading to reduced blood pressure: up to 6 mmHg systolic and 3 mmHg diastolic
Elevation of HDL cholesterol, with no effect on total and LDL cholesterol
Inhibition of platelet aggregation and activation, leading to fewer blood clots that cause heart attacks and strokes
Decreased inflammation
Reduction of C-reactive protein, a marker of inflammation
Decreased neutrophil (white blood cell) activation. White blood cells play a role in inflammation
Decreased LDL cholesterol oxidation, leading to fewer atherosclerotic complications
Improved function of the cells that line blood vessels (endothelium)
Possible enhanced insulin sensitivity
May act as anti-carcinogens and neuro-protective agents
May act as an antidepressant

Note also that low-fat natural non-alkalized cocoa powder is also a rich source of antioxidant flavonoids.

Bottom line? Dark chocolate, especially because of flavonoids, may well be protective against cardiovascular disease such as heart attacks and strokes.

[Did you notice I’m waffling . . . may be protective.]

What’s in dark chocolate other than flavonoids?

A 40 gram serving of a fine dark chocolate bar has:

Calories: 200
Calories from fat: 150
Fiber: 4.5 grams (dark chocolate is a good source of fiber on a “per calorie” basis)
Sugar: 11 grams
Saturated fats: 10 grams

But aren’t saturated fats bad for me?

The fats in dark chocolate are 1/3 oleic (healthy monounsaturated, as in olive oil), 1/3 stearic (saturated, but no effect on cholesterol levels, unlike some other saturated fats), and 1/3 palmitic (saturated, and could increase cholesterol levels and heart risk). So it’s sort of a wash.

[I’m not getting into the diet-heart hypothesis now. Don’t bait me.]

What’s the healthy “dose” of dark chocolate?

No one is sure. It’s certainly no more than 100 grams (3.5 ounces) a day, and the optimal dose may be as low as 20 grams every three days. If you eat too much, it will make you fat. 100 grams is 500 calories; that’s probably way too much. Even if you start eating 20 grams – 100 calories – every three days, you will gain weight unless you give up some other food or exercise a little more.

Parker, why are you waffling?

Because no one has ever done a study to see if adding dark chocolate actually reduces death rates or sickness from specific diseases in humans. I think it probably does, but who knows for sure? Nobody. What we need is a randomized, controlled trial of dark chocolate as a supplement in 10,000 middle-aged adults followed over the course of 10 years. I’d sign up for that in a heartbeat. Just don’t give me the placebo.

Steve Parker, M.D.

Additional Resources:

Clay Gordon, author of the book Discover Chocolate, kindly critiqued an early version of this blog post here. If the link doesn’t work, go to The Chocolate Life and search “Health Benefits of Chocolate” in the Forums.

References:

Erdman, J.W., et al. Effects of cocoa flavanols on risk factors for cardiovascular disease. Asian Pacific Journal of Clinical Nutrition, 17 supplement 1 (2008): 284-287.

Farouque, H.M, et al. Acute and chronic effects of flavanol-rich cocoa on vascular function in subjects with coronary artery disease: a randomized double-blind placebo-controlled study. Clinical Science, 111 (2006): 71-80.

Heptinstall, S., et al. Cocoa flavanols and platelet and leukocyte function: recent in vitro and ex vivo studies in healthy adults. Journal of Cardiovascular Pharmacology, 47 supplement 2 (2006): S197-205.

Keen, C.L., et al. Cocoa antioxidants and cardiovascular health. American Journal of Clinical Nutrition, 81 supplement 1 (2005): 298S-303S.

Mehrinfar, R. and Frishman, W.H. Flavanol-rich cocoa: a cardioprotective nutraceutical. Cardiology Reviews, 16 (2008): 109-115.

Engler, M.B, and Engler, M.M. The emerging role of flavonoid-rich cocoa and chocolate in cardiovascular health and disease. Nutrition Reviews, 64 (2006): 109-118.

Lippi, G. et al. Dark chocolate: consumption for pleasure or therapy? Journal of Thrombosis and Thrombolysis, September 23, 2008 (Epub ahead of print).

Hooper, L, et al. Flavonoids, flavonoid-rich foods, and cardiovascular risk: a meta-analysis of randomized controlled trials. American Journal of Clinical Nutrition, 88 (2008): 38-50.

Cooper, K.A., et al. Cocoa and health: a decade of research. British Journal of Nutrition, 99 (2007): 1-11. Epub August 1, 2007.

Aron, P.M., and Kennedy, J.A. Flavon-3-ols: nature, occurrence and biological activity. Molecular Nutrition and Food Research, 52 (2008): 79-104.

Buijsse, B, et al. Cocoa intake, blood pressure, and cardiovascular mortality [in men]: the Zutphen Elderly Study. Archives of Internal Medicine, 166 (2006): 411-417.

Ding, E.L., et al. Chocolate and prevention of cardiovascular disease: a systematic review. Nutrition and Metabolism, 3 (2006): 2.

Comments Off on Health Benefits of Dark Chocolate

Posted in Chocolate

Tagged cardiovascular disease, chocolate, dark chocolate, heart disease

If Dark Chocolate Is Healthy, What’s The Right Dose?

Posted on June 3, 2012 | Comments Off

Antioxidant flavonoids and other phytonutrients in dark chocolate are thought possibly to improve health, primarily through reduction in cardiovascular diseases such as heart attacks and strokes. I previously blogged about these and other potential health benefits of dark chocolate.

In terms of a medicinal agent, we have not been sure of the therapeutic “dose.” A recent study out of Italy provides a clue.

Researchers at Catholic University, Campobasso, Italy, surveyed residents in southern Italy regarding chocolate intake and measured their C-reactive protein (CRP) levels. CRP is a marker of inflammation and a predictor of coronary artery disease such as heart attacks. Generally, higher levels of CRP are associated with higher risk of heart attacks. If you have a choice, go for lower levels of CRP.

Methodology

Participants in the study were selected by simple random sampling from city hall registries and were at least 35 years old. Researchers were looking for healthy people, so the following were excluded from the study: those who reported known cardiovascular disease, eating a special diet, or on drug therapy for high blood pressure, diabetes, or adverse blood lipids. Twenty percent of initial recruits refused to participate. Of the 10,994 initial recruits, 4,849 men and women made it into the final study.

Of the 4,849 subjects, two subgroups were identified: 1) a control group of 1,317 (27%) who never ate any type of chocolate, and 2) a test group of 824 (17%) subjects who regularly ate dark chocolate only.

Interviewers administered questionnaires to the subjects to document clinical and personal information such as dietary habits, socioeconomic status, physical activity, medical history, risk factors for cardiovascular disaese and tumors, family history of cardiovascular disease, drug use, etc.

Regarding chocolate consumption, participants were asked about frequency – daily, weekly, or monthly – of a “standard dose” (20 grams) and about type of chocolate: milk, dark, nut chocolate, or any type. Someone eating more than one type of chocolate was classified as “any type.”

Other measurements: blood pressure, weight, height, waist circumference, blood glucose, serum lipids (various cholesterols and triglycerides), and high-sensitivity C-reactive protein.

Findings

Age-adjusted CRP levels were lower in dark chocolate users (1.13 mg/L) than in the nonconsumers of chocolate (1.30 mg/L).

Dark chocolate eaters were divided into thirds: the lowest third of average consumption, the middle third, and the highest third. The lowest third ate under 19 grams per week. The middle third ate between 19 and 47 grams per week. The highest third ate over47 grams per week. The chocolate-related reduction in CRP was lost in people who were in the highest third (or tertile), i.e., eating more than 47 grams a week or 20 grams every three days. People in the lowest tertile of dark chocolate consumption had a CRP reduction the same as the middle third.

Systolic blood pressure in dark chocolate consumers was 3 mmHg lower than the pressure in nonconsumers. No difference in diastolic pressures.

Discussion

The researchers cite two clinical trials that investigated the effect of cocoa on markers of inflammation but did not find any association. They wonder if those studies enrolled too few participants, or whether the relatively high doses of chocolate masked the effect. In the present study, the lowering of CRP was seen in consumption of up to 20 grams every three days, but seemed to disappear at higher doses.

The authors write that:

. . . regular intake of small amounts of dark chocolate . . . consumption should have no harmful effect on anthropometric variables such as BMI [body mass index] and waist:hip ratio and can be viewed as a promising behavioural approach to lower, in a quite pleasant way, cardiovascular risk factors at a general population level.

According to data reported in apparently healthy American men and women, ranges of serum CRP measured in our nonchocolate consumer population would belong to a “moderate” risk estimate quintile, whereas the ranges found in dark chocolate consumers would be classified as a “mild” risk estimate. For the decrease in serum CRP values from moderate to mild quintile, the relative risk of suffering a future cardiovascular event would apparently decrease by 26% in men and 33% in women.

The authors are careful to point out that this study does not prove that low-dose dark chocolate lowers CRP levels. It’s an association. “Additional studies are necessary to explain the mechanisms linking dark chocolate consumption and regulation of serum CRP concentrations.”

My Comments

The healthy dose of dark chocolate may be quite small: no more than 20 grams every three days, and perhaps quite a bit less. This is not much by U.S. standards. The serving size listed on many bars here is 40 grams. Forty grams has about 200 calories. Twenty grams twice a week translates to 29 calories a day.

The authors of this study don’t address whether 40 grams a week would be just as healthy as 80 grams every two weeks.

Eating more, on average, than 20 grams every three days may entirely wipe out the healthy effects. This effect is like wine’s: a little is probably good for you, too much is either neutral or harmful.

I’m sorry to be so wishy-washy on this issue, but that’s the state of the science today. The study at hand may help us optimize dark chocolate’s effect on C-reactive protein. But dark chocolate’s other healthy effects may require other doses, higher or lower.

The next step is to take 20,000 middle-aged people, give half of them various doses of scheduled dark chocolate, give the other half placebos, then record rates of diseases and death over the next 10 years. Who would pay for this multi-million dollar study? Either government or chocolate manufacturers.